Oral care compositions for active agent delivery

ABSTRACT

An oral care composition with an aqueous phase, hydrophobic phase, active agent, and optionally emulsifier. A jammed emulsion with aqueous phase, hydrophobic phase, active agent, and optionally emulsifier. An oral care composition with aqueous phase, hydrophobic phase, active agent, and optionally emulsifier. Methods of using disclosed compositions for active agent delivery.

FIELD OF THE INVENTION

The present invention relates to oral care compositions for the deliveryof active agents, such as bleaching agents. The present invention alsorelates to hydrophobic phase in hydrophilic phase (i.e. oil-in-water)emulsion compositions for the delivery of active agents, such asbleaching agents. The present invention also relates to jammedoil-in-water emulsions for the delivery of active agents, such asbleaching agents.

BACKGROUND OF THE INVENTION

Teeth can become discolored by the deposition of stains due to exposureto coffee, wine, cola, or other drinks and foods. Thus, consumers desiremethods and compositions to whiten teeth. Compositions comprising anactive agent, such as peroxide compounds, can be effective at whiteningteeth. For example, the nightguard vital tooth bleaching technique with10% carbamide peroxide (equivalent to 3.3 wt % hydrogen peroxide) hasbeen used to whiten teeth. However, the use of carbamide peroxide athigh concentrations still required a long treatment regimen, such asovernight wear, and produced undesirable side effects, such as toothsensitivity and soft tissue irritation. Since then, many whiteningprocedures have been developed, but utilized higher concentrations ofperoxide compounds, such as greater than 3.3 wt % of hydrogen peroxide,which produced faster whitening times, but led to more frequent and moresevere tooth sensitivity.

The introduction of high viscosity gel compositions based on hydrogenperoxide improved the retention of the hydrogen peroxide within thebleaching trays and increased the adhesiveness of the hydrogen peroxideto the surface of the teeth through the use of carboxypolymethylenecompounds, such as Carbopol®. Unfortunately, the gel compositionscomprising a carboxypolymethylene compound dehydrated the surface of theteeth and interacted with the hydrogen peroxide, which led to a netslowing of the whitening process and led to increased occurrence andseverity of tooth sensitivity.

One strategy to mitigate the dehydration of the surface of teeth was touse a hydrophilic phase in hydrophobic phase emulsion (discontinuousaqueous droplets suspended in a continuous hydrophobic medium, such asoil). The aqueous phase droplets included high concentrations ofhydrogen peroxide, such as 35%, which corresponded to a lower totalconcentration of hydrogen peroxide over the entire emulsion composition.These hydrophilic in hydrophobic emulsions allowed the hydrogen peroxideto rapidly migrate to the hydrophilic tooth surface to yield highperformance whitening with minimal side effects. Since the peroxidecomposition, in terms of the entire emulsion, was lower than acorresponding single-phase composition comprising 35% hydrogen peroxide,tooth sensitivity and gum irritation were dramatically reduced oreliminated. In other words, the aqueous phase in hydrophobic emulsionsled to targeted peroxide delivery. However, the performance of thehydrophilic in hydrophobic emulsions were limited by the whiteningpotential of the aqueous droplets closest to the tooth surface.

Thus, there is a need for a composition that can effectively whitenteeth without the negative side effects commonly associated with highconcentrations of peroxide compounds.

SUMMARY OF THE INVENTION

Disclosed herein is an oral care composition comprising jammed emulsion,the jammed emulsion comprising (a) at least partially continuous aqueousphase; (b) discontinuous hydrophobic phase; and (c) oral care activeagent.

Disclosed herein is an oral care composition comprising jammed emulsion,the jammed emulsion comprising (a) from about 1% to about 20%, by weightof the composition, of at least partially continuous aqueous phase; (b)from about 80% to about 99%, by weight of the composition, ofdiscontinuous hydrophobic phase; and (c) oral care active agent.

Disclosed herein is an oral care composition, such as an oil-in-wateremulsion, preferably comprising high internal phase emulsion, even morepreferably comprising jammed emulsion, the oral care compositioncomprising (a) from about 0.01% to about 20%, by volume of thecomposition, of an at least partially continuous aqueous phase; (b) fromabout 80% to about 99%, by volume of the composition, of a discontinuoushydrophobic phase; (c) optionally an emulsifier; and (d) from about0.01% to about 10%, by weight of the composition, of oral care activeagent.

Disclosed herein is an oral care composition comprising (a) from about1% to about 20%, by weight of the composition, of an at least partiallycontinuous aqueous phase, wherein the aqueous phase has a first initialviscosity; (b) from about 80% to about 99%, by weight of thecomposition, of a discontinuous hydrophobic phase, wherein thehydrophobic phase has a second initial viscosity; (c) optionally anemulsifier; and (d) from about 0.01% to about 1%, by weight of thecomposition, of an oral care active agent, wherein the composition has afinal viscosity that is greater than the first initial viscosity and/orthe second initial viscosity.

Disclosed herein is an oral care composition comprising (a) from about1% to about 20%, by weight of the composition, of an at least partiallycontinuous aqueous phase, wherein the aqueous phase has a first initialyield stress; (b) from about 80% to about 99%, by weight of thecomposition, of a discontinuous hydrophobic phase, wherein thehydrophobic phase has a second initial yield stress; (c) an emulsifier;and (d) from about 0.01% to about 1%, by weight of the composition, ofan oral care active agent, wherein the composition has a final yieldstress that is greater than the first initial yield stress and/or thesecond initial yield stress.

Disclosed is an oral care composition comprising (a) from about 1% toabout 20%, by weight of the composition, of an at least partiallycontinuous aqueous phase; (b) from about 80% to about 99%, by weight ofthe composition, of a discontinuous hydrophobic phase; (c) anemulsifier; and (d) from about 1% to about 10%, by weight of thecomposition, of an oral care active agent, wherein the composition isstable to macroscopic separation for at least 48 hours at 23° C.

Also disclosed herein are methods of using the oral care compositions,as described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows the stable jammed oil-in-water emulsion of Example I-A(84% hydrophobic phase).

FIG. 1B shows the stable jammed oil-in-water emulsion of Example I-B(90.4% hydrophobic phase).

FIG. 1C shows the stable jammed oil-in-water emulsion of Example I-C(94% hydrophobic phase).

FIG. 1D shows the stable jammed oil-in-water emulsion of Example I-D(96.5% hydrophobic phase).

FIG. 1E shows the stable jammed oil-in-water emulsion of Example I-E(97.5% hydrophobic phase).

FIG. 2 shows the macroscopic separation of Comparative Example 1 (74%hydrophobic phase).

FIG. 3A shows the microscope image of the stable jammed oil-in-wateremulsion of Example I-A (84%).

FIG. 3B shows the microscopic image of the stable jammed oil-in-wateremulsion of Example I-B (90.4%).

FIG. 3C shows the microscopic image of the stable jammed oil-in-wateremulsion of Example I-C (94%).

FIG. 3D shows the microscopic image of the stable jammed oil-in-wateremulsion of Example I-D (96.5%).

FIG. 3E shows the microscopic image of the stable jammed oil-in-wateremulsion of Example I-E (97.5%).

FIG. 4A shows the macroscopic separation of Comparative Example II(3.43% Tween 60).

FIG. 4B shows the stable jammed oil-in-water emulsion of Example I-F(3.43% Tween 20).

FIG. 5 shows the macroscopic separation of Comparative Example III(3.43% Tween 40).

FIG. 6A shows the macroscopic separation of Comparative Example IV wherethe hydrophobic phase was added in a single addition.

FIG. 6B shows the stable jammed oil-in-water emulsion of Example I-Fwhere the hydrophobic phase was added sequentially with mixing aftereach addition.

FIG. 7 shows Example II as a cohesive semi-solid bead when dispensedfrom a tube.

FIG. 8A shows macroscopic separation of Comparative Example V (Span 20as an emulsifier).

FIG. 8B shows the stable jammed oil-in-water emulsion of Example III(Tween 20 as an emulsifier).

FIG. 9A shows a microscopic image of Comparative Example VI as awater-in-oil emulsion with discrete droplets of aqueous phase dispersedin the hydrophobic phase.

FIG. 9B shows Example I-B as a jammed oil-in-water emulsion with regionsof oil dispersed in the aqueous phase.

FIG. 10A shows a microscopic image of Comparative Example VII as awater-in-oil emulsion with discrete droplets of aqueous phase dispersedin the hydrophobic phase.

FIG. 10B shows Example I-B as a jammed oil-in-water emulsion withregions of oil dispersed in the aqueous phase.

FIG. 11 shows Example I-B as a jammed oil-in-water emulsion after 90days at 40° C.

FIG. 12A shows the average decrease in yellowness against a baseline(left) after a single treatment with Example I-B delivered on a tray incombination with electromagnetic radiation.

FIG. 12B shows the highest decrease in yellowness against a baseline(left) after a single treatment with Example I-B delivered on a tray incombination with electromagnetic radiation.

FIG. 13 shows 1) a holder for the microscope slides, 2) 9 microscopeslides, 3) tape securing the slides to the holder, and 4) a samplesketch of a bead of a multi-phase oral care composition or hydrophobicphase applied to one of the slides.

FIG. 14 shows 3 beads for 2 batches of Example I-B, and 3 beads of thevalidation composition for the slide flow method specified herein afterit has been tilted at 45 degrees for 60 seconds. This image shows thatthe beads have barely flowed down the slides for Example I-B, but flowedall the way to the bottom of the slide for the validation compositionfor the slide flow method specified herein.

FIG. 15 shows the template and a coverslip that can be used to load amulti-phase composition of the present invention for observation under amicroscope.

FIG. 16A shows the macroscopic separation within one hour of ComparativeExample VIII being made where the minor aqueous phase was added to themajor hydrophobic phase.

FIG. 16B shows the stable jammed oil-in-water emulsion of Example I-Bwhere the major hydrophobic phase was added to the minor aqueous phase.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to hydrophobic phase in hydrophilicphase emulsions for delivering oral care active agents, such as, forexample, bleaching agents, to the oral cavity. Additionally, the presentinvention is directed to high internal phase emulsions preferably jammedemulsions for the delivery of oral care active agents, such as, forexample, bleaching agents, to the oral cavity.

The current invention further improves the whitening performance ofmultiphase compositions, such as hydrophilic phase in hydrophobic phaseemulsions (i.e. water-in-oil emulsions). The current invention maintainsthe improved tolerability relative to single-phase compositions, whileincreasing the efficiency of the oral care active agent delivery.

In a water-in-oil emulsion, discrete regions or small droplets of theaqueous phase comprising an active agent are dispersed in a continuoushydrophobic phase, such as oil. While not wishing to be bound by theory,the whitening performance of water-in-oil emulsion systems can belimited by how many aqueous droplets from within the discontinuous phasecan reach the surface of teeth. Merely switching to an oil-in-wateremulsion, where discrete droplets of a hydrophobic phase are dispersedthroughout a predominant continuous aqueous phase comprising an oralcare active agent, such as a bleaching agent, can lead to severe toothsensitivity and gum irritation due to a high total concentration of oralcare active agents or whitening agents, such as peroxide compounds.

Surprisingly, the oil-in-water emulsion system can be structured inmanner such that the aqueous phase becomes a thin continuous phasebetween distinct regions of the hydrophobic phase (referred to as ajammed oil-in-water emulsion). In certain aspects of jammed oil-in-wateremulsions, the hydrophilic or aqueous phase is the minor component andthe hydrophobic phase, despite being the discontinuous phase, is themajor component. Microscopically, regions of continuous aqueous phaseappear as a thin continuous phase surrounding discrete hydrophobicregions.

Importantly, jammed oil-in-water emulsion have several advantagesrelative to water-in-oil emulsions. For example, water-in-oil emulsionshave a discontinuous aqueous phase of droplets in a hydrophobic phase.In the water-in-oil emulsions, only the droplets that migrate to thetooth surface are involved in the active agent delivery process.Additionally, there is no rapid interaction between aqueous dropletswithout external forces to create movement within the water-in-oilemulsion. In contrast, the high internal phase emulsions, preferablyjammed oil-in-water emulsions of the present invention, the aqueousphase can comprise regions of continuous phase. While not wishing to bebound by theory, it is believed that once any portion of the aqueousphase contacts a tooth surface, the relatively thinner continuous regionof aqueous phase can continuously deliver the entire amount of theactive agent or bleaching agent to the tooth surface. As the agent isdelivered to the tooth surfaces, in certain aspects, the continuity ofthe aqueous phase enables replenishment of the agent to the surface fromthe aqueous phase throughout. Surprisingly, even though regions ofcontinuous aqueous phase are able to replenish the surface with theactive agent, it is still sufficiently rate limited in the deliveredamount of agent per unit contact area as to not exceed the tolerabilitythresholds of the surfaces. For example, a jammed oil-in-water emulsionwith 35% hydrogen peroxide in the aqueous phase is able to be safelyapplied to the hard and soft tissues with far less irritation thanapplying an equivalent amount of a 35% aqueous solution to the softtissues which can cause unwanted and excessive irritation of the softtissues as the dose per unit area will exceed the ability of the softtissues to dilute and decompose the peroxide before it can cause theunwanted tissue effects.

Jammed oil-in-water emulsions have several advantages over traditionaloil-in-water emulsions. For example, in a traditional oil-in-wateremulsion, a minority discontinuous hydrophobic phase is stabilized in amajority continuous aqueous phase. Delivering an active agent, such as ableaching agent, from a majority continuous aqueous phase can lead totooth sensitivity and gum irritation when using the high concentrationsof bleaching agent needed to quickly and effectively whiten teeth.

Importantly, merely combining a minority aqueous phase with a majorityhydrophobic phase will not necessarily lead to a jammed oil-in-wateremulsion. In fact, in most cases, combining a minority aqueous phasewith a majority hydrophobic phase will lead to a water-in-oil emulsionwith discrete droplets of aqueous phase dispersed in the hydrophobicphase, or macroscopic separation.

Surprisingly, as described herein, it was found that by adding thepredominant hydrophobic phase to the less predominant hydrophilic phase,a jammed oil-in-water emulsion can be prepared. It is counter intuitiveto add the major hydrophobic component to the minor hydrophiliccomponent. The jammed emulsion can be prepared by adding a portion ofthe hydrophobic phase to the hydrophilic phase followed by mixing andthen repeating the procedure until all of the hydrophobic phase has beenadded to the hydrophilic phase.

Alternatively, the hydrophobic phase may be added in a continuous orpulsed fashion to the hydrophilic phase under constant stirringconditions until all of the hydrophobic phase has been added. Withoutwishing to be bound by theory, when the hydrophobic phase reaches acertain volume percentage of the total emulsion (i.e. the jammingconcentration), the emulsion begins to jam. When the jamming of theemulsion occurs, the viscosity of the emulsion can increase, and theemulsion can become more physically stable. Physical stability of theemulsion can be important to prevent macroscopic separation during thestorage of the composition. In contrast, it was surprisingly found thataddition of the minor hydrophilic phase to the major hydrophobic phasecan lead to macroscopic separation, even when the minor hydrophilicphase is added in a portion-wise manner coupled with mixing.

Without not wishing to be bound by theory it was surprisingly found thatbleaching agents can be effective in very low concentrations, ifpresented in a multi-phase oral care composition as disclosed herein.The present invention comprises an oral care composition comprising anemulsion, preferably a jammed oil-in-water emulsion, the preferredjammed oil-in-water emulsion comprising an aqueous phase, a hydrophobicphase, and from about 0.01% to about 10% of at least one oral careactive agent.

Definitions

By “oral care composition”, as used herein, is meant a product that itis retained in the oral cavity for a time sufficient to contact dentalsurfaces or oral tissues. Examples of oral care compositions includedentifrice, tooth gel, subgingival gel, mouth rinse, mousse, foam, mouthspray, lozenge, chewable tablet, chewing gum, tooth whitening strips,floss and floss coatings, breath freshening dissolvable strips, denturecare products, or denture adhesive products. The oral care compositionmay also be incorporated onto strips, trays or films for directapplication or attachment to oral surfaces.

The term “dentifrice”, as used herein, includes tooth orsubgingival-paste, gel, or liquid formulations unless otherwisespecified. The dentifrice composition may be a single-phase compositionor may be a combination of two or more separate dentifrice compositions.The dentifrice composition may be in any desired form, such as deepstriped, surface striped, multilayered, having a gel surrounding apaste, or any combination thereof. Each dentifrice composition in adentifrice comprising two or more separate dentifrice compositions maybe contained in a physically separated compartment of a dispenser anddispensed side-by-side.

The term “immiscible” or “insoluble” as used herein means less than 1part by weight of the substance dissolves in 100 parts by weight of asecond substance.

The term “solubility” as used herein is the maximum number of parts byweight of the substance that can dissolve in 100 parts by weight of asecond substance.

The term “phase” as used herein means a physically distinct region orregions, which may be continuous or discontinuous, having one or moreproperties that are different from another phase. Non-limiting examplesof properties that may be different between phases include composition,viscosity, solubility, hydrophobicity, hydrophilicity, visualcharacteristics, and miscibility. Examples of phases include solids,semisolids, liquids, and gases.

The term “multi-phase oral care composition” as used herein comprises amixture of two or more phases that are immiscible with each other, forexample water-in-oil, oil-in-water emulsions, or mixtures thereof. Thephases may be continuous, discontinuous, or combinations thereof. Themulti-phase oral care composition or a phase of the multi-phase oralcare composition may be solid, liquid, semisolid, or combinationsthereof. In preferred aspects the multi-phase oral care composition issemisolid. Examples of multi-phase oral care compositions also includecompositions where the phases are multi-continuous includingbi-continuous, layered, striped, marbled, ribbons, swirled, andcombinations thereof. Examples of multi-phase oral care compositionsalso include compositions where the phases are tessellated or tiled.

The term “emulsion” as used herein is an example of a multi-phase oralcare composition wherein: 1) at least one of the phases is discontinuousand 2) at least one of the phases is continuous. Examples of emulsionsinclude droplets of oil dispersed in water. In this example, the waterand oil would be mutually immiscible with each other, oil would be thediscontinuous phase, and the water would be the continuous phase.

The term “macro-emulsion” as used herein is an example of an emulsionwherein at least one of the discontinuous phases is visible under amicroscope using light with one or more wavelengths from 400 nm to 700nm. Examples of macro-emulsions include those in which the mass mediandiameter, volume weighted mean diameter, or surface weighted meandiameter of the regions of at least one of the discontinuous phases islarger than the wavelength of light being used, for instance larger than0.1, 0.4, or 0.7 micron.

The term “micro-emulsion” as used herein is an example of an emulsionwherein the discontinuous phases is not visible under a microscope usinglight with one or more wavelengths from 400 nm to 700 nm. Examples ofmicro-emulsions include those in which the regions of the discontinuousphases are smaller than the wavelength of light being used, for instancesmaller than 0.1, 0.4, or 0.7 micron.

The term “oil-in-water emulsion” as used herein is an example of anemulsion wherein 1) the continuous phase is aqueous or hydrophilic, and2) the discontinuous phase is hydrophobic.

The term “water-in-oil emulsion” as used herein is an example of anemulsion wherein 1) the continuous phase is hydrophobic, and 2) thediscontinuous phase is aqueous or hydrophilic.

The term “high internal phase emulsion” as used herein is an example ofan emulsion wherein the discontinuous phase comprises more than about74% by weight or volume of the multi-phase oral care composition. Highinternal phase emulsions may be oil-in-water emulsions, water-in-oilemulsions, or mixtures thereof.

The term, “jammed emulsion” as used herein, is a high internal phaseemulsion 1) wherein the high internal phase emulsion exhibits no morethan 5% macroscopic separation after 48 hours at 23° C. measuredaccording to the method specified herein, and/or 2) wherein separateregions of discontinuous phase influence the shape of one another.Examples of jammed emulsions may include high internal phase emulsionsin which adjacent or neighboring regions of discontinuous phaseinfluence the shape of one another.

The term “jamming concentration” of a high internal phase emulsion asused herein is the minimum concentration of the discontinuous phaseabove which the high internal phase emulsion 1) exhibits no more than 5%macroscopic separation after 48 hours at 23° C. measured according tothe method specified herein, and/or 2) wherein separate regions ofdiscontinuous phase influence the shape of one another.

The term “jam” or “jamming” of a high internal phase emulsion as usedherein is the phenomenon where the high internal phase emulsiontransitions to one that 1) exhibits no more than 5% macroscopicseparation after 48 hours at 23° C. measured according to the methodspecified herein and/or 2) wherein separate regions of discontinuousphase influence the shape of one another.

The term “solid” as used herein is a material that, at roomtemperature, 1) has defined dimensions even when it is not constrainedin a container, or 2) maintains its original shape when it is picked upoff a surface and subsequently placed back on the surface.

The term “liquid” as used herein is a material that, at roomtemperature, 1) flows under gravity, or 2) takes the shape of thecontainer it is placed in. Examples of liquids include mineral oil,water, and silicone oil. When a liquid is poured into a container, theexposed surface (the surface that is not in contact with the walls ofthe container) of liquids may become horizontal and flat due to gravity.Liquids may have a freezing point, melting point or drop melting pointas measured according to ASTM method D127 or a congealing point asmeasured according to ASTM method D938 or a pour point as measuredaccording to ASTM D97 less than about OC, less than about 23° C., orless than about 40° C. Liquids may have a kinematic viscosity measuredaccording to ASTM D445 at 40° C. less than about 10,000 cSt, less thanabout 1000 cSt, or less than about 100 cSt.

The term “semisolid” as used herein is a material that, at roomtemperature, 1) has some solid-like properties and some liquid-likeproperties, or 2) whose ability to meet the above definition of a solidor liquid may depend on the amount of material being evaluated; forexample, a small amount of petrolatum placed in a large container maynot flow under gravity, and it may not take the shape of the container(thus not meeting the definition of a liquid); but a large amount ofpetrolatum placed in an large container may flow under gravity, or itmay take the shape of the container (thus meeting the definition of aliquid). Examples of semisolids include petrolatum, toothpaste, siliconegels, mayonnaise, butter, lotions, creams, ointments, and jammedemulsions.

The term “lotion” as used herein is a preparation intended forapplication on the body, surfaces of the oral cavity, or mucosalsurfaces. Examples of lotions include hand lotions, skin care lotions,body lotions, suntan lotions, and jammed emulsions.

The term “aqueous phase” as used herein is a phase that comprises water,optionally at least one active agent, and is immiscible with thehydrophobic phase.

The term “hydrophobic phase” as used herein means all components of thecomposition that are immiscible with the aqueous phase.

The term “equivalent-diameter” of a region or droplet as used hereinmeans the diameter of a sphere having the same volume as the region ordroplet.

The term “Dv 50 equivalent-diameter” as used herein is theequivalent-diameter in microns at which 50% of the regions ofhydrophobic phase or droplets of aqueous phase are smaller and 50% arelarger. The v in the term Dv 50 shows that this refers to the volumedistribution. The Dv 50 equivalent-diameter of regions of hydrophobicphase of a multi-phase oral care composition is measured according tothe method specified herein.

The term “D[4,3] equivalent-diameter” as used herein is thevolume-weighted-mean equivalent-diameter in microns of the regions ofhydrophobic phase or droplets of aqueous phase. The D[4,3]equivalent-diameter of regions of hydrophobic phase of a multi-phaseoral care composition is measured according to the method specifiedherein.

The term “D[3,2] equivalent-diameter” as used herein is thesurface-weighted-mean equivalent-diameter in microns of the regions ofhydrophobic phase or droplets of aqueous phase. The D[3,2]equivalent-diameter of regions of hydrophobic phase of a multi-phaseoral care composition is measured according to the method specifiedherein.

The term “two-dimensional density of droplets of aqueous phase” as usedherein means the number of droplets of aqueous phase a) that are presentin a square centimeter of a two-dimensional plane in the multi-phaseoral care composition and b) wherein the cross-sectional area of thedroplets of the aqueous phase in the two-dimensional plane are largerthan a specified value.

The term “two-dimensional density of regions of hydrophobic phase” asused herein means the number of regions of hydrophobic phase a) that arepresent in a square centimeter of a two-dimensional plane in themulti-phase oral care composition and b) wherein the cross-sectionalarea of the regions of hydrophobic phase in the two-dimensional planeare larger than a specified value.

The term “cone penetration consistency value” as used herein means thedepth, in tenths of a millimeter, that a standard cone will penetratethe sample under fixed conditions of mass, time, and temperature. Thecone penetration consistency value is measured according to ASTM methodD937.

The term “delivery carrier” as used herein comprises a material or anappliance that is used to hold the multi-phase oral care compositionagainst the tooth surface. Examples of delivery carriers include stripsor dental trays.

The term “strip” as used herein comprises a material 1) whose longestdimension length is generally greater than its width, and 2) whose widthis generally greater than its thickness. Strips may be rectangular,arched, curved, semi-circular, have rounded corners, have slits cut intoit, have notches cut into it, bent into three dimensional shapes, orcombinations thereof. Strips may be solid, semisolid, textured,moldable, flexible, deformable, permanently deformable, or combinationsthereof. Strips may be made from plastic sheets including polyethylene,or wax sheets. Examples of strips include a piece of polyethylene about66 mm long, 15 mm wide and 0.0178 mm thick. Examples of permanentlydeformable strips include a piece of casting wax sheet about 66 mm long,15 mm wide, and 0.4 mm thick.

The term “rinseable” as used herein means the material can be rinsedfrom a surface using water at a certain temperature in a certain periodof time. Examples of rinseable materials generally include honey, milk,and compositions comprising oil-in-water emulsions such as Examples I-A,I-B, I-C, I-D, I-E, and I-F below.

The term “dispersible” as used herein means the material can bedispersed in water at a certain temperature. The water-dispersibility ofthe material is measured according to the method specified herein.Examples of water-dispersible materials generally include compositionscomprising oil-in-water emulsions such as Examples I-A, I-B, I-C, I-D,I-E, and I-F below.

The term “macroscopic separation” as used herein is a phenomenon inwhich at least a portion of one or more components or one or more phasesof a composition separates out of the composition. The macroscopicseparation is measured according to the method specified herein. Thelack of macroscopic separation is a measure of the physical stability ofa composition.

The term “heterogenous mixture” as used herein is a heterogenouscombination of two or more substances. Examples of heterogenous mixturesinclude emulsions such as oil-in-water emulsions, and jammed emulsions.Heterogenous mixtures do not include homogenous mixtures (such assolutions where a solute is uniformly dissolved in a solvent).

The term “heterogenous dispersion” as used herein is a heterogenouscombination of two or more substances Examples of heterogenousdispersions include emulsions such as oil-in-water emulsions, and jammedemulsions. Heterogenous dispersions do not include homogenousdispersions (such as solutions where a solute is uniformly dissolved ina solvent).

The term “petrolatum” as used herein means a semisolid mixture ofhydrocarbons. Petrolatum may have a cone penetration consistency valueas measured according ASTM method D937 from about 10 to about 500,preferably from about 25 to about 300, more preferred from about 50 toabout 250, or more preferred from about 100 to about 200. Petrolatum mayhave a melting point or drop melting point as measured according to ASTMmethod D127 or a congealing point as measured according to ASTM methodD938 from about from about 40° C. to about 120° C., preferably fromabout 50° C. to about 100° C., more preferred from about 50° to about90° C., or more preferred from about 60° C. to about 80° C.

The term “mineral oil” as used herein means a liquid mixture ofhydrocarbons. Mineral oil may have a cone penetration consistency valueas measured according ASTM method D937 more than about 600, preferablymore than about 500, or more preferred more than about 400. Mineral oilmay have a freezing point, melting point or drop melting point asmeasured according to ASTM method D127 or a congealing point as measuredaccording to ASTM method D938 or a pour point as measured according toASTM D97 less than about 0° C., less than about 23° C., or less thanabout 40° C. Mineral oil may have a kinematic viscosity measuredaccording to ASTM D445 at 40° C. less than about 10,000 cSt, less thanabout 1000 cSt, or less than about 100 cSt.

The term “HLB” of an emulsifier is an expression of itsHydrophile-Lipophile Balance, i.e. the balance of the size and strengthof the hydrophilic (water-loving or polar) and the lipophilic (oilloving or non-polar) groups of the emulsifier. The HLB values arequantified as follows:

-   -   A. For non-ionic emulsifiers (except those containing propylene        oxide, butylene oxide, nitrogen, or sulfur) HLB values are        calculated according to the procedure specified in “The HLB        system—a time-saving guide to emulsifier selection”, from ICI        Americas, Wilmington Del. 19897, which is herein incorporated in        its entirety by reference, including the various emulsifiers and        blends of multiple emulsifiers listed in it along with their HLB        values.    -   B. For ionic emulsifiers HLB values are calculated according to        the procedure specified in 1) “A quantitative kinetic theory of        emulsion type I, physical chemistry of the emulsifying agent”        by J. T. Davies J. H. Schulman (Ed.), Proceedings of the 2nd        International Congress on Surface Activity, Academic Press, New        York (1957), 2) Davies, J. T. (1959) Proc. Int. Congr. Surf.        Act., 1, 426, and/or 3) Davies, J. T. and Rideal, E. K. (1961)        Interfacial Phenomena.    -   C. For all other emulsifiers and those whose HLB values cannot        be calculated according to either of the above two procedures,        HLB values are measured experimentally according to the        experimental procedure specified in “The HLB system—a        time-saving guide to emulsifier selection”, from ICI Americas,        Wilmington Del. 19897.

As used herein, the word “or” when used as a connector of two or moreelements is meant to include the elements individually and incombination; for example X or Y, means X or Y or both.

As used herein, the articles “a” and “an” are understood to mean one ormore of the material that is claimed or described, for example, “an oralcare composition” or “a bleaching agent.”

The term “safe and effective amount” as used herein means an amount of acomponent, high enough to significantly (positively) modify thecondition to be treated or to affect the desired whitening result, butlow enough to avoid serious side effects (at a reasonable benefit/riskratio), within the scope of sound medical/dental judgment. The safe andeffective amount of a component, will vary with the particular conditionbeing treated, the age and physical condition of the patient beingtreated, the severity of the condition, the duration of treatment, thenature of concurrent therapy, the specific form employed, and theparticular vehicle from which the component is applied.

The term “a sufficient period of time to achieve whitening” as usedherein is meant that the composition is used or worn by the participantor the participant is instructed to use or wear the composition forgreater than about 10 seconds; or greater than about 1 minute, such asfrom about 2.5 minutes to about 12 hours (for example overnighttreatment), or from about 3 minutes to about 180 minutes; or greaterthan about 5 minutes, such as from about 5 minutes to about 60 minutes;or greater than about 10 minutes, such as from about 10 minutes to about60 minutes; or from about 1, 5, 10, or 15 minutes to about 20, 30, 60,120 minutes per application; or any other numerical range, which isnarrower and which falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein. Inaddition, the treatments may be applied from about 1, 2, or 3 times aday to about 4, 5, 6 or 7 times a day. The treatments may be applied forfrom about 1, 2, 3, 4, 5, 6, or about 7 days to about 8, 9, 10, 11, 12,13, 14, 21, or 28 days or any other numerical range, which is narrowerand falls within such broader numerical range, as if such narrowernumerical ranges were all expressly written herein. Further, the lengthof treatment to achieve the desired benefit, for example, toothwhitening, may last for a specified period of time, which may berepeated if necessary, for example from about one day to about sixmonths, from about one day to about 28 days, or from about 7 to about 28days. The optimal duration and frequency of application will depend onthe desired effect, the severity of any condition being treated, thehealth and age of the patient and like considerations.

The term “dispenser”, as used herein, means any pump, tube, or containersuitable for dispensing oral care compositions.

All percentages and ratios used herein after are by weight of totalcomposition (wt %), unless otherwise indicated. All percentages, ratios,and levels of ingredients referred to herein are based on the actualamount of the ingredient, and do not comprise solvents, fillers, orother materials with which the ingredient may be combined as acommercially available product, unless otherwise indicated.

All measurements referred to herein are made at about 23° C.+/−1° C.(i.e. room temperature) unless otherwise specified.

All parameters that have a method specified herein are measured usingthe method specified herein, unless otherwise specified.

“Active and other ingredients” useful herein may be categorized ordescribed herein by their cosmetic and/or therapeutic benefit or theirpostulated mode of action or function. However, it is to be understoodthat the active and other ingredients useful herein can, in someinstances, provide more than one cosmetic and/or therapeutic benefit orfunction or operate via more than one mode of action. Therefore,classifications herein are made for the sake of convenience and are notintended to limit an ingredient to the particularly stated function(s)or activities listed.

The term “teeth”, as used herein, refers to natural teeth as well asartificial teeth or dental prosthesis and is construed to comprise onetooth or multiple teeth. The term “tooth surface” as used herein, refersto natural tooth surface(s) as well as artificial tooth surface(s) ordental prosthesis surface(s) accordingly.

The term “orally acceptable carrier” comprises one or more compatiblesolid or liquid excipients or diluents which are suitable for use in theoral cavity. By “compatible,” as used herein, is meant that thecomponents of the composition are capable of being commingled withoutinteraction in a manner which would substantially reduce thecomposition's stability and/or efficacy.

While specific reference is made to “consumers” or “patients,”throughout the specification, these terms are used interchangeably torefer to any user of the multi-phase oral care composition. The consumeror patient can apply the composition to the oral cavity themselves, orhave the composition applied to their oral cavity by a third party, suchas a dentist, hygienist, orthodontist, ‘or other medical or dentalprofessional.

Jammed Emulsions

As described herein, the present invention relates to multi-phase oralcare compositions for the delivery of active agents, such as bleachingagents. The multi-phase oral care composition, as described herein,comprises a high internal phase emulsion, or preferably a jammedoil-in-water emulsion.

Traditional oil-in-water emulsions are multi-phase compositions with adiscontinuous hydrophobic phase and a continuous aqueous phase. Stableoil-in-water emulsions can be prepared by combining a minorityhydrophobic phase with a majority aqueous phase. Traditionaloil-in-water emulsions are discontinuous droplets of hydrophobic phasesuspended and/or stabilized within a continuous aqueous phase. As thehydrophobic and aqueous phases are immiscible, generally only a smallportion of the hydrophobic phase can be stabilized within the aqueousphase before macroscopic separation occurs.

A high internal phase emulsion can be either oil-in-water orwater-in-oil emulsion, wherein there is a high amount of the internal,discontinuous phase, by volume or weight of the multi-phase composition,relative to a traditional emulsion. A high internal phase emulsion canhave more of the internal, discontinuous phase, by volume or weight ofthe total multi-phase composition than the external, continuous phase,by volume or weight of the multi-phase composition. However, thestability of high internal phase emulsions can prove challenging. Highinternal phase emulsions can suffer from macroscopic separation uponmixing or during storage of the high internal phase emulsions prior touse by a consumer.

As described herein, a jammed emulsion may be an unexpectedly stablehigh internal phase emulsion. As the concentration of the discontinuousphase of a high internal phase emulsion is increased, regions ofdiscontinuous phase can become sufficiently crowded, such that they canjam against each other with a region of continuous phase between themand deform each other with a region of continuous phase between them. Ifboth the continuous phase and discontinuous phase are liquids, theemulsion can transition into an at least a partially semisolid structurewhen the jamming transition occurs.

For example, FIG. 9A shows a microscopic image of Comparative ExampleVI, which comprises a water-in-oil emulsion, while FIG. 9B is amicroscopic image of Example I-B, which comprises a jammed oil-in-wateremulsion. The comparison of the images visually shows the structuraldifferences between a water-in-oil emulsion and a jammed oil-in-wateremulsion that can contribute to the stability of jammed oil-in-wateremulsions.

For convenience, the jammed oil-in-water emulsions, as described herein,can be represented or described in two dimensions along an x-y plane.Additionally, the jammed emulsions can appear two-dimensional in a lightmicroscope, such as in FIG. 9B, due to the focal plane. However, it isto be understood that jammed emulsions are three-dimensional.

Examples of jammed emulsions include those in which, under amicroscope, 1) regions of discontinuous phase are or resemblepolyhedrons or polygons, with or without rounded corners, with visiblejamming between regions of discontinuous phase, with continuous phasesandwiched between regions of discontinuous phase, 2) regions ofdiscontinuous phase are or resemble non-spherical shapes, with visiblejamming between regions of discontinuous phase, with continuous phasesandwiched between regions of discontinuous phase, 3) regions ofdiscontinuous phase are in a tessellated or tiled pattern or resembleone, with continuous phase sandwiched between regions of discontinuousphase, or 4) regions of discontinuous phase are in a pattern thatresemble a Voronoi diagram with continuous phase sandwiched betweenregions of discontinuous phase. Examples of jammed emulsions includethose in which 1) the cone penetration consistency value or the slideflow distance of the emulsion is less than that of the continuous phaseand/or discontinuous phase, or 2) the kinematic viscosity, BrookfieldViscosity, yield stress, shear storage modulus, shear loss modulus, orratio of the shear storage modulus to the shear loss modulus of theemulsion is more than that of the continuous phase and/or discontinuousphase. Examples of jammed emulsions include those in which, under amicroscope, regions of discontinuous phase are or resemble polyhedronsor polygons, with or without rounded corners, with from about 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 to about 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, or 16 substantially straight sides orsubstantially flat surfaces with visible jamming between regions ofdiscontinuous phase, with continuous phase sandwiched between regions ofdiscontinuous phase. Examples of jammed emulsions include those inwhich, under a microscope, portions of regions of discontinuous phaseare or resemble polyhedrons or polygons, with or without roundedcorners, with from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, or 16 to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or16 substantially straight sides or substantially flat surfaces withvisible jamming between regions of discontinuous phase, with continuousphase sandwiched between regions of discontinuous phase.

The jammed emulsion, as described herein, can be prepared by theportion-wise addition or gradual addition or slow addition of thediscontinuous phase to the continuous phase. Simply combining the entirediscontinuous phase to the continuous phase will not necessarily resultin jammed emulsion. A Voronoi diagram can be used to describe and/orillustrate the preparation of a jammed emulsion. For example, asportions of the discontinuous phase are added to the continuous phase,molecules of the discontinuous phase will associate into the closestregions to minimize entropically unfavorable hydrophobic-hydrophilicinteractions. Without wishing to be bound by theory, it is believed thatadding the entire discontinuous phase to the continuous phase,macroscopic separation will be more likely to occur. Instead, by slowlyadding (either by portion-wise addition or a slow continuous addition),the molecules of the discontinuous phase can associate into discreteregions instead of separating macroscopically. As the concentration ofthe discontinuous phase reaches the jamming concentration, a jammingtransition can occur where separate regions of the discontinuous phasecan influence the shapes of one another (for example neighboring oradjacent regions of discontinuous phase), which can contribute to theunexpected stability of jammed emulsions. In certain aspects of jammedemulsions, 1) separate regions of the discontinuous phase can influencethe shape of one another (for example neighboring or adjacent regions ofdiscontinuous phase), which can lead to a transition from substantiallyspherical discontinuous regions to at least partially polyhedraldiscontinuous regions at the jamming concentration, or 2) the emulsioncan exhibit a Yield Stress or Brookfield Viscosity greater than that ofthe constituent aqueous phase and/or the hydrophobic phase measuredaccording to the methods specified herein at 23° C.

The multi-phase oral care compositions, as described herein, can berinseable with water at a reasonable temperature in a suitable amount oftime. A reasonable temperature for the jammed emulsion to be rinseablewith water is a water temperature that would be easily accessed from awater source at a residential location without having to further heatthe water upon initial collection at a residential water source, such asfor example, a water temperature of from about 4° C. to about 60° C.,from about 20° C. to about 50° C., from about 10° C. to about 50° C., upto about 60° C., or less than about 50° C. A suitable amount of time torinse the jammed emulsion out of a delivery device is dependent on thetemperature of water. For example, a suitable amount of time caninclude, for example, up to 30 about minutes, up to about 20 minutes,from about 1 second to about 5 minutes, from about 5 seconds to about 1minute, less than about 1 minute, or less than about 30 seconds.Preferably, the water rinseability of the multi-phase oral carecomposition at 23° C. can be up to about 10 minutes, up to about 5minutes, up to about 1 minute, or up to 30 seconds.

The multi-phase oral care compositions can be described by itswater-dispersibility according to the method disclosed herein. The waterdispersibility of the multi-phase oral care composition can be measuredat any suitable temperature of up to about 60° C. The waterdispersibility of the multi-phase oral care composition can be greaterthan about 5%, greater than about 10%, greater than about 20%, greaterthan about 25%, or greater than about 50% of the total content of themulti-phase oral care composition, by weight or volume. Preferably, thewater-dispersibility of the multi-phase oral care compositions asmeasured at 23° C. can be from about 20% to 100%, from about 40% to100%, from about 60% to 100%, or greater than about 70%, by weight orvolume of the total multi-phase oral care composition.

The multi-phase oral care compositions, as described herein, maycomprise high internal phase emulsion, or preferably jammed oil-in-wateremulsion. The jammed oil-in-water emulsions comprise hydrophobic phase,aqueous phase, active agent, and optionally emulsifier.

The multi-phase oral compositions of the present invention may be aheterogenous mixture and/or heterogenous dispersion. The multi-phaseoral composition, aqueous phase, or hydrophobic phase of the presentinvention can be substantially free of an added adhesive, preferablysubstantially free of an added hydrophilic adhesive (for examplehydrophilic particles that become sticky when activated by moisture) oran added hydrophilic substantivity agent, and preferably substantiallyfree of an added hydrophilic liquid adhesive (for example glycerin). Ifthe multi-phase oral composition of the present invention comprises anadded adhesive, added hydrophilic adhesive, added hydrophilic liquidadhesive, added hydrophilic substantivity agent, added hydrophilicactive releasing agent, or added hydrophilic peroxide releasing agent,it may be present in a range from about 0, 0.1, 0.2, 0.4, 1, 2, 3, 4, 5,to about 0, 0.1, 0.2, 0.4, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20% or anyother numerical range which is narrower and which falls within suchbroader numerical range, as if such narrower numerical ranges were allexpressly written herein; preferably less than about 20%, morepreferably less than about 10%, even more preferably less than about 5%,or most preferably less than about 0.5% by weight of the multi-phaseoral composition

It is worth noting that stick type products may be unhygienic forrepeated use inside the oral cavity due to potential contamination orbio-film build-up. Saliva or moisture may penetrate into the stick typecomposition when used inside the oral cavity and this may degrade theactive agents especially bleaching agents such as peroxides duringstorage between uses; and this degradation may be further accelerated byenzymes present in saliva. Furthermore, this degradation could be mostpronounced at the tip of the stick type product that comes in directcontact with the saliva or moisture inside the oral cavity, leading todiminished efficacy the next time the stick type product is used. This“contact-degrade-contact” cycle may be repeated every time the sticktype product is used—leading to most if not all applications after thefirst application being less efficacious. It is also worth noting thatstick type products may need an added active releasing agent or addedperoxide releasing agent to improve the release of the active orperoxide trapped in the stick type product. In general, active releasingagents or peroxide releasing agents are hydrophilic water-soluble orwater-swellable polymers or hydrophilic liquids that may providehydration channels in the composition allowing water to penetrate thecomposition and allowing the active or peroxide component to leach out.However, these channels may also allow more saliva to penetrate into thecomposition which may accelerate the degradation of the active orperoxide.

It is worth noting that multi-phase oral compositions in liquid form mayexhibit macroscopic separation of one or more components due todifferences in the density of the phases. Specifically, liquidcompositions that are particles or droplets dispersed in one or moreliquids may exhibit macroscopic separation of one or more components dueto the difference in density of the particles or droplets compared tothe one or liquids they are dispersed in. Furthermore, multi-phase oralcompositions in liquid form may not be substantive and run down theteeth or run out of the delivery carrier during application or duringuse.

Thus, in certain aspects of the multi-phase oral compositions of thepresent invention, the stick type product or liquid form is lesspreferable or not preferred.

Multi-phase oral compositions of the present invention may be a liquid,paste, cream, gel, ointment, semisolid, lotion, or any combinationthereof; preferably a semisolid or a lotion. Multi-phase oralcompositions of the present invention may be easy to dispense from atube as determined by the method specified herein.

It is also worth noting that some product forms, especially stick typeproducts, may need an added active releasing agent or added peroxidereleasing agent to improve the release of the active or peroxide trappedin the stick type product. In general, active releasing agents orperoxide releasing agents are hydrophilic water-soluble orwater-swellable polymers or hydrophilic liquids that may providehydration channels in the composition allowing water to penetrate thecomposition and allowing the active or peroxide to leach out. An addedperoxide releasing agent (such as sodium percarbonate) may help breakthe hydrophobic matrix as a result of micro bubbles that may begenerated when the it comes in contact with water; and this disruptionmay enhance the release of the whitening agents, such as the hydrogenperoxide. However, it has been surprisingly discovered that themulti-phase oral compositions of the present invention can beself-releasing (for example, they release active or peroxide evenwithout an added active releasing agent or an added peroxide releasingagent). Without wishing to be bound by theory, it is hypothesized thatthe multi-phase oral compositions of the present invention can beself-releasing because the aqueous phase (which may comprise activeagent or bleaching agent) comprises an at least partially continuousphase that may be exposed directly to the hydrophilic tooth surface—thisin turn may release the active agent or bleaching agent with little orimpediment from the hydrophobic phase. Thus, the multi-phase oralcomposition, aqueous phase, or hydrophobic phase of the presentinvention can be preferably substantially free of an added activereleasing agent or added peroxide releasing agent, more preferablysubstantially free of an added hydrophilic active releasing agent oradded hydrophilic peroxide releasing agent (for example water-soluble orwater-swellable polymers, hydrophilic liquids, or sodium percarbonate).In certain aspects, the multi-phase oral composition of the presentinvention and/or the hydrophobic phase of the present invention can beself-releasing (i.e. they release active or peroxide even without anadded active releasing agent or an added peroxide releasing agent).

The multi-phase oral composition, aqueous phase, or hydrophobic phase ofthe present invention can be substantially free of an added wax since itmay promote the formation of stick type products that are less or notpreferred.

The multi-phase oral composition, aqueous phase, or hydrophobic phase ofthe present invention can be substantially free of ingredients, such asbleaching agents, that may react with other ingredients.

The multi-phase oral composition, aqueous phase, or hydrophobic phase ofthe present invention can be substantially free of ingredients, forexample abrasives, silica, fumed silica, sodium tripolyphosphate,polyorganosiloxanes, condensation products of silicone resins andorganosiloxanes, polymers of styrene, polymers of ethylene, polymers ofpropylene, polyvinylpyrrolidone, glycerin, tin fluoride, or combinationsthereof, that at temperatures (for example −7° C., 4° C., 23° C., 25°C., 30° C., 40° C., 50° C., or 60° C.) and conditions that themulti-phase oral composition may be exposed to during manufacture,filling, shipping, or storage (for example 1 day, 2 days, 1 week, 2weeks, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, or24 months) prior to use by the consumer 1) may compromise the efficacy,comfort, usage experience, concentration of actives or bleaching agentsat the tooth surface over time, active or bleaching efficiency, orcompatibility between ingredients, or 2) may react with otheringredients, degrade other ingredients, cause foam or pressure to buildup, decrease the substantivity of the multi-phase oral composition toteeth, cause the multi-phase oral composition to thicken or harden, ormake it difficult or impractical to manually dispense a suitable dose ofthe multi-phase oral composition from a tube, or cause one or morecomponents of the multi-phase oral composition to macroscopicallyseparate.

The multi-phase oral composition, aqueous phase, or hydrophobic phase ofthe present invention can be substantially free of fumed silica since itmay decrease the stability of the bleaching agent.

The multi-phase oral composition may be easy to manually dispense from atube after 1 day, 2 days, 1 week, 2 weeks, 1 month, 2 months, 3 months,6 months, 12 months, 18 months, or 24 months at −7° C., 4° C., 23° C.,25° C., 30° C., 40° C., 50° C., or 60° C.

The Product Information document (Form No. 52-1052B-01, Aug. 9, 2016)from the supplier (Dow Corning Corporation) states that BIO-PSA StandardSilicone Adhesives are supplied using heptane or ethyl acetate as asolvent—both of which have a strong odor making them unappealing to usein the oral cavity. Thus, the multi-phase oral composition, aqueousphase, or hydrophobic phase of the present invention can besubstantially free of ingredients with a strong odor for examplealcohols, solvents, ethyl acetate, heptane, or ingredients with aboiling point less than 99° C. The multi-phase oral composition, aqueousphase, or hydrophobic phase of the present invention can besubstantially free of ingredients, for example silicone adhesives,cyclic silicones, silicones, silicone fluids, dimethicone, paraffinumliquidum, mixtures of silicones with hydrocarbons, mixtures of liquidsilicones with liquid hydrocarbons, trimethylsiloxysilicate/dimethiconolcrosspolymers, or combinations thereof, that at temperatures (forexample −7° C., 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or 60°C.) and conditions that the multi-phase oral composition may be exposedto during manufacture, filling, shipping, or storage (for example 1 day,2 days, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 12months, 18 months, or 24 months) prior to use by the consumer 1) maycompromise the efficacy, comfort, usage experience, concentration ofactives or bleaching agents at the tooth surface over time, active orbleaching efficiency, or compatibility between ingredients, or 2) mayreact with other ingredients, degrade other ingredients, cause foam orpressure to build up, decrease the substantivity of the multi-phase oralcomposition to teeth, cause the multi-phase oral composition to thickenor harden, or make it difficult or impractical to manually dispense asuitable dose of the multi-phase oral composition from a tube, or causeone or more components of the multi-phase oral composition tomacroscopically separate.

The multi-phase oral composition, aqueous phase, or hydrophobic phase ofthe present invention can be substantially free of structure-buildingagents, for example amphiphilic co-polymers such aspolyvinylpyrrolidone-vinyl acetate, polyvinylpyrrolidone-co-polyvinylbutyrate, or polyvinylpyrrolidone-co-polyvinyl propionate co-polymers,that may not only thicken the oral care composition, but may also drivethe oral care composition toward a homogenous state or maintain the oralcare composition in a homogenous state. This is becausestructure-building agents such as amphiphilic co-polymers 1) have atleast one monomer that is hydrophilic and this may make the multi-phaseoral composition more susceptible to being washed away in saliva orother liquids, or 2) may drive the oral care composition toward ahomogenous state and this may decrease the concentration of actives orbleaching agents at the tooth surface over time.

Aqueous Phase

The multi-phase oral care compositions, high internal phase emulsions,or jammed oil-in-water emulsions, as described herein, comprise aqueousphase. The aqueous phase can be at least partially continuous,essentially continuous, or preferably continuous.

The multi-phase oral care composition comprises from about 0.01% toabout 25%, from about 1% to about 20%, from about 2.5% to about 20%, orpreferably from about 5% to about 15%, by weight or volume of themulti-phase oral care composition or jammed oil-in-water emulsion, ofthe aqueous phase.

The aqueous phase may also include other water-soluble solvents, such asfor example, polyalkylene glycols with molecular weights from about 200to about 20,000, humectants, or combinations thereof. Suitablehumectants generally include edible polyhydric alcohols such asglycerin, sorbitol, xylitol, butylene glycol, and propylene glycol, andmixtures thereof. The aqueous phase may comprise at least about 10%, atleast about 20%, or at least about 30%, of water, by weight or volume ofthe aqueous phase.

The multi-phase oral care compositions, as described herein, maypredominantly comprise a jammed oil-in-water emulsion. However, a smallportion of the multi-phase composition can comprise droplets of aqueousphase, optionally comprising an active agent. The size of the dropletsof the aqueous phase, if present, may be a factor to decreaseoral/topical irritation and/or tooth-sensitivity. For example, withoutwishing to be being bound by theory, if there are droplets of theaqueous phase present in the multi-phase oral care composition, if thesize of the droplets of the aqueous phase is too large it may lead tolarge spots on oral/topical/tooth surfaces that are exposed to a highconcentration of the active agent, which can lead to oral/topicalirritation and/or tooth-sensitivity. Thus, the multi-phase oral carecomposition can be described by the Dv 50 equivalent-diameter, D[4,3]equivalent-diameter, or D[3,2] equivalent-diameter of the droplets ofaqueous phase. For example, the Dv 50 equivalent-diameter, D[4,3]equivalent-diameter, or D[3,2] equivalent-diameter of the droplets ofaqueous phase can be from about 0.1 to 5000, from about 0.1 to about500, or from about 1 to about 50 microns.

Multi-phase oral care compositions that have a high density of largedroplets of aqueous phase may lead to oral/topical irritation and/ortooth-sensitivity. Thus, it can be advantageous to minimize the densityof the large droplets of aqueous phase to minimize oral/topicalirritation and/or tooth-sensitivity. The method specified herein tomeasure the “two-dimensional density of droplets of aqueous phase” canbe used to measure the droplets in two dimensions—this can be done usinga light microscope by counting the number of droplets larger than aspecified size (at the focal plane). For example, the two-dimensionaldensity of droplets of aqueous phase larger than 10000 square micronsfound in 1 cm² of the multi-phase oral care composition can be up toabout 1, up to about 0.1, or preferably 0. Preferably, the multi-phaseoral care composition can be free of or substantially free of dropletsof aqueous phase with a cross-sectional area of up to about 1000, 3000,10000, 20000, or 50000 square microns.

The multi-phase oral compositions may comprise an aqueous solution of ableaching agent, such as hydrogen peroxide, optionally includingemulsifier.

Hydrophobic Phase

The multi-phase oral care compositions or high internal phase emulsions,preferably jammed oil-in-water emulsions, as described herein, comprisea hydrophobic phase. The hydrophobic phase is at least partiallydiscontinuous, essentially discontinuous, or preferably discontinuous.

The present invention comprises a safe and effective amount of ahydrophobic phase. The multi-phase oral care composition comprises fromabout 75% to about 99%, from about 80% to about 97.5%, greater thanabout 80%, greater than about 90%, or preferably, from about 85% toabout 95%, by weight or volume of the multi-phase oral care compositionor jammed oil-in-water emulsion, of the hydrophobic phase.

The density of the hydrophobic phase used in the multi-phase oral carecompositions, as described herein, may be in the range of from about 0.8g/cm³ to about 1.0 g/cm³, from about 0.85 g/cm³ to about 0.95 g/cm³, orabout 0.9 g/cm³, or any other numerical range, which is narrower, andwhich falls within such broader numerical range, as if such narrowernumerical ranges were all expressly written herein.

The hydrophobic phase can comprise a non-toxic oil, such as non-toxicedible oil. The hydrophobic phase can comprise non-toxic edible oils,saturated or unsaturated fatty alcohols, aliphatic hydrocarbons, longchain triglycerides, fatty esters, and combinations thereof. Thehydrophobic phase may also comprise silicones, polysiloxanes, andmixtures thereof. The hydrophobic phase may be preferably selected frommineral oil, petrolatum, and combinations thereof. A preferredpetrolatum is white petrolatum. Other examples of petrolatum includeSnow White Pet-C from Calumet Specialty Products (Indianapolis, Ind.),G-2191 from Sonneborn (Parsippany, N.J.), G-2218 from Sonneborn, G-1958from Sonneborn, G-2180 from Sonneborn, Snow White V28 EP from Sonneborn,and Snow White V30 from Sonneborn, G-2494 from Sonneborn, and mixturesthereof.

The multi-phase oral compositions may comprise discontinuous phase,which can comprise mineral oil. The multi-phase oral compositions maycomprise hydrophobic phase, which can comprise mineral oil as ahydrophobic phase.

The aliphatic hydrocarbons can comprise from about 10, 12, 14, or 16 toabout 16, 18, 20, 22, 24, 26, 28, 30, 36, 40 carbon atoms such asdecane, 2 ethyldecane, tetradecane, isotetradecane, hexadecane,eicosane, and combinations thereof. Long chain triglycerides cancomprise vegetable oils, fish oils, animal fats, hydrogenated vegetableoils, partially hydrogenated vegetable oils, semi-synthetictriglycerides, synthetic triglycerides, and mixtures thereof.Fractionated, refined or purified oils of these types can also be used.Examples of long chain triglyceride-containing oils include almond oil;babassu oil; borage oil; black currant seed oil; canola oil; castor oil;coconut oil; corn oil; cottonseed oil; emu oil; evening primrose oil;flax seed oil; grapeseed oil; groundnut oil; mustard seed oil; oliveoil; palm oil; palm kernel oil; peanut oil; rapeseed oil; safflower oil;sesame oil; shark liver oil; soybean oil; sunflower oil; hydrogenatedcastor oil; hydrogenated coconut oil; hydrogenated palm oil;hydrogenated soybean oil; hydrogenated vegetable oil; a mixture ofhydrogenated cottonseed oil and hydrogenated castor oil; partiallyhydrogenated soybean oil; a mixture of partially hydrogenated soybeanoil and partially hydrogenated cottonseed oil; glyceryl trioleate;glyceryl trilinoleate; glyceryl trilinolenate; a Ω3-polyunsaturatedfatty acid triglyceride containing oil; and mixtures thereof. The longchain triglyceride containing oils may be selected from the groupconsisting of corn oil, olive oil, palm oil, peanut oil, safflower oil,sesame oil, soybean oil, castor oil, linseed oil, rape oil, rice branoil, coconut oil, hydrogenated castor oil; partially hydrogenatedsoybean oil; glyceryl trioleate; glyceryl trilinoleate; aΩ3-polyunsaturated fatty acid triglyceride containing oil; andcombinations thereof.

Saturated or unsaturated fatty alcohols may have from about 6 to about20 carbon atoms, cetearyl alcohol, lauryl alcohol, and mixtures thereof.For example, Lipowax (Cetearyl Alcohol and Ceteareth-20) are suppliedand manufactured by Lipo Chemical.

General information on silicones including silicone fluids, gums andresins, as well as the manufacture of silicones, can be found inEncyclopedia of Polymer Science and Engineering, Volume 15, SecondEdition, pp 204-308, John Wiley & Sons Inc. 1989 and Chemistry andTechnology of Silicones, Walter Noll, Academic Press Inc, (Harcourt BrueJavanovich, Publishers, New York), 1968, pp 282-287 and 409-426.

The multi-phase oral care compositions, aqueous phase, or hydrophobicphase may be substantially free of ingredients, for example acids and/oralcohols, combinations of mineral oil and ethylene/propylene/styrenecopolymer and/or butylene/ethylene/styrene copolymer, certain bleachingagents, fumed silica, polyorganosiloxanes, copolymer condensationproducts of silicone resins and polydiorganosiloxanes, or combinationsthereof, silicones, dimethicone, paraffinum liquidum,trimethylsiloxysilicate/dimethiconol crosspolymer, or combinationsthereof, molecules with double or triple covalent bonds between adjacentcarbon atoms, molecules with styrene groups, that at temperatures (forexample −7° C., 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or 60°C.) and conditions that the multi-phase oral care composition may beexposed to during manufacture, filling, shipping, or storage (forexample 1 day, 2 days, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6months, 12 months, 18 months, or 24 months) prior to use by the consumerthat 1) may compromise the efficacy, comfort, usage experience,concentration of actives or bleaching agents at the tooth surface overtime, active or bleaching efficiency, or compatibility betweeningredients, or 2) may react with other ingredients or degrade otheringredients or may cause foam or pressure to build up in the package orcontainer in which the multi-phase oral care composition is stored. Themulti-phase oral care compositions may comprise less than 0.001% byweight of the composition, of any of the compounds recited in thisparagraph, preferably multi-phase oral care compositions do not compriseacids and/or alcohols. Without being bound by a theory it is believedthat the decrease in surface tension produced by alcohol may decreasethe retention time of the aqueous phase at the tooth surface, therebydecreasing the efficacy of the oral care actives. The presence of acidsmight contradict with the actives and/or may produce negative sideeffects as the tooth surface such as hypersensitivity etc. Thus, themulti-phase oral care compositions can be free of acids, free ofalcohols, or free of a mixture thereof.

The hydrophobic phase is in predominant or majority proportion relativeto the aqueous phase present in the multi-phase oral care composition.As used herein “predominant proportion” means that the percent by weightor volume of the hydrophobic phase of the multi-phase oral carecomposition is in excess relative to the percent by weight or volume ofthe aqueous phase of the multi-phase oral care composition.

The size and number of regions of hydrophobic phase may affect theamount of oral/topical irritation and/or tooth sensitivity imparted bythe multi-phase oral composition, or stability of the multi-phase oralcomposition. The multi-phase oral care composition can be described interms of its “two-dimensional density of regions of hydrophobic phase”measured using the method specified herein. For example, thetwo-dimensional density of regions of hydrophobic phase larger thanabout 10, 100, 1000, or preferably 10000 μm² found in 1 cm² of themulti-phase oral care composition can be from about 1 to about1,000,000, from about 10 to 100,000, or preferably, from about 100 toabout 10,000.

Similarly, the multi-phase oral care composition can be described by theDv 50 equivalent-diameter, D[4,3] equivalent-diameter, or D[3,2]equivalent-diameter of regions of the hydrophobic phase. For example,the Dv 50 equivalent-diameter, D[4,3] equivalent-diameter, or D[3,2]equivalent-diameter of regions of the hydrophobic phase can be fromabout 0.1 to 5000, from about 0.1 to about 500, or preferably from about1 to about 50 microns.

The hydrophobic phase may be inert or at least partially inert. Thehydrophobic phase may interact, not interact, or only minimally interactwith the other ingredients of the multi-phase oral care compositions,such as for example, flavors, thickeners, or the active agents.

A suitable hydrophobic phase for the compositions as disclosed hereinmay have an octanol/water partition coefficient (log P_(ow)) of greaterthan about 2, 3, 4, 5, or greater than about 5.5, as determined by OECD117, Partition Coefficient (n-octanol/water), HPLC method. Additionally,the hydrophobic phase can show a log P_(ow) greater than about 6, asdetermined by OECD 117.

Without being bound by theory, the freezing point, melting point or dropmelting point as measured according to ASTM method D127, or congealingpoint as measured according to ASTM method D938, or pour point asmeasured according to ASTM D97 of the hydrophobic phase may be a factorto ensure that the composition: 1) is substantive and does not run downthe teeth or run out of the delivery carrier during application orduring use, 2) inhibits macroscopic separation of one or more of thecomponents of the multi-phase oral care composition at a particularoperating, handling, storage, or manufacturing temperature, such as, forexample, 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or 60° C., for aparticular period of time, such as, for example, 1 day, 2 days, 1 week,2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, 18 months, or24 months, prior to use by the consumer, or 3) releases an effectiveamount of the bleaching agent or active agent during use.

Specifically, if the freezing point, melting point or drop melting pointas measured according to ASTM method D127, or congealing point asmeasured according to ASTM method D938, or pour point as measuredaccording to ASTM D97 of the hydrophobic phase is too low, themulti-phase oral care composition may not be substantive and run downthe teeth or run out of the delivery carrier during application orduring use; or the multi-phase oral care composition may exhibitmacroscopic separation of one or more of the components of themulti-phase oral care composition at temperatures and conditionsexperienced prior to use by consumer, as described herein. In contrast,if the freezing point, melting point or drop melting point as measuredaccording to ASTM method D127, or congealing point as measured accordingto ASTM method D938, or pour point as measured according to ASTM D97 ofthe hydrophobic phase is too high, the multi-phase oral care compositionmay not release an effective amount of the bleaching agent or activeagent during use.

The freezing point, melting point or drop melting point as measuredaccording to ASTM method D127, or congealing point as measured accordingto ASTM method D938, or pour point as measured according to ASTM D97 ofthe hydrophobic phase may be from about −100° C. to about 100° C., −50°C. to about 23° C., or preferably from about −50° C. to about 0° C. Thefreezing point, melting point or drop melting point as measuredaccording to ASTM method D127, or congealing point as measured accordingto ASTM method D938, or pour point as measured according to ASTM D97 ofthe hydrophobic phase may be less than about 40° C., 30° C., 23° C., 10°C., 0° C., −10° C., −20° C., −30° C., 40° C., −50° C., or −100° C. orany other numerical range, which is narrower, and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein.

Without being bound by theory, the cone penetration consistency value,kinematic viscosity, Brookfield Viscosity, yield stress, shear storagemodulus, shear loss modulus, ratio of the shear storage modulus to theshear loss modulus, or slide flow distance of the hydrophobic phasealone or the multi-phase oral care composition in total may be a factorto ensure that the multi-phase oral care composition: 1) is substantiveand does not run down the teeth or run out of the delivery carrierduring application or during use, 2) inhibits macroscopic separation ofone or more of the components of the multi-phase oral care compositionat a particular operating, handling, storage, or manufacturingtemperature, such as, for example, 4° C., 23° C., 25° C., 30° C., 40°C., 50° C., or 60° C., for a particular period of time, such as, forexample, 1 day, 2 days, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6months, 12 months, 18 months, or 24 months, prior to use by theconsumer, or 3) releases an effective amount of the bleaching agent oractive agent during use.

Specifically, if the cone penetration consistency value or the slideflow distance of the hydrophobic phase or the multi-phase oral carecomposition is too high, or the kinematic viscosity, BrookfieldViscosity, yield stress, shear storage modulus, shear loss modulus, orratio of the shear storage modulus to the shear loss modulus is too low,the multi-phase oral care composition may not be substantive and rundown the teeth or run out of the delivery carrier during application orduring use; or the multi-phase oral care composition may exhibitmacroscopic separation of one or more of the components of themulti-phase oral care composition at temperatures and conditionsexperienced prior to use by consumer, as described herein. In contrast,if the cone penetration consistency value or the slide flow distance ofthe hydrophobic phase or the multi-phase oral care composition is toolow, or the kinematic viscosity, Brookfield Viscosity, yield stress,shear storage modulus, shear loss modulus, or ratio of the shear storagemodulus to the shear loss modulus of the hydrophobic phase or themulti-phase oral care composition is too high, the multi-phase oral carecomposition may not release an effective amount of the bleaching agentor active agent during use.

It is worth noting that, in general: 1) hydrophobic phases that have alow cone penetration consistency value tend to form stick type products,especially when combined with powder ingredients including active agentsor bleaching agents that are ground or manufactured to minimize particlesize e.g. by micronization, 2) hydrophobic phases that are rich in waxestend to have a low cone penetration consistency value, 3) stick typeproducts tend to have a low cone penetration consistency value, 4)hydrophobic phases that have a low cone penetration consistency value(that tend to form stick type products) may also inhibit the release ofthe bleaching agent or active agent, and 5) stick type products (thattend to have a low cone penetration consistency value) may also inhibitthe release of the bleaching agent or active agent. It is also worthnoting that multi-phase oral compositions that have a low conepenetration consistency value or multi-phase oral compositions whosehydrophobic phase has a low cone penetration consistency value may bedifficult or impractical to manually dispense a suitable dose of themulti-phase oral composition from a tube.

Thus, in certain aspects, the cone penetration consistency value of thehydrophobic phase or multi-phase oral compositions may have a conepenetration consistency value as measured according ASTM method D937more than about 600, more than about 500, or more than about 400.

The Brookfield Viscosity of the hydrophobic phase or multi-phase oralcare composition can be from about 10 cPs to about 5,000,000 cPs, fromabout 1,000 cPs to about 500,000 cPs, from about 1,000 cPs to about100,000 cPs, or preferably from about 1,000 cPs to about 50,000 cPs asmeasured at 23° C. according to the method specific herein. TheBrookfield Viscosity of the multi-phase oral care composition can be atleast 2, 5, 10, 25, 50, 100, 200, and/or 250 times greater than theinitial viscosity of the aqueous phase and/or the hydrophobic phase.

The kinematic viscosity of the hydrophobic phase or multi-phase oralcare composition can be from about 1 mm²/s to about 10,000 mm²/s, fromabout 1 mm²/s to about 1,000 mm²/s, or preferably from about 5 mm²/s toabout 500 mm²/s as measured by ASTM D 445 at 40° C.

The ratio of the shear storage modulus to the shear loss modulus of themulti-phase oral care composition can be from about 0.01 to about 2,from about 0.5 to 2, or preferably from about 1 to about 2.

The slide flow distance of the multi-phase oral care composition orhydrophobic phase can be up to about 30 mm, up to about 20 mm, up toabout 10 mm, or preferably from about 0 mm to about 10 mm as measuredaccording to the method specified herein.

The yield stress of the multi-phase oral care composition can be fromabout 2 Pa to about 2000 Pa, from about 2 Pa to about 500 Pa, orpreferably from about 2 Pa to about 250 Pa as measured according to themethod specified herein at 23° C.

Active Agents

The present multi-phase oral care compositions or high internal phaseemulsions preferably jammed oil-in-water emulsions, as described herein,comprise a safe and effective amount of one or more active agents,preferably oral care active agents.

One or more active agents can be dissolved, at least partiallydissolved, or dispersed in the aqueous phase, hydrophobic phase, orcombinations thereof. One or more active agents can be in the aqueousphase and one or more active agents can be in the hydrophobic phase,depending on whether the active agent is more soluble in the aqueous orhydrophobic phase.

The oral care active agent can comprise one or more active agents, suchas an anti-caries agent, an anti-tartar agent, a remineralization agent,a wound healing agent, an anti-inflammatory agent, an antibacterialagent, a metal ion source, an anti-glycolytic agent, an amino acid, aprobiotic, a prebiotic, a postbiotic, a polyphosphate, a buffer,anti-sensitivity agent, a bleaching agent, or combinations thereof.

Many of the oral care active agents can have more than one use, whichcan allow specific oral care actives to fall within more than onecategory. For example, a fluoride salt, such as stannous fluoride, canbe an anti-caries agent, a metal ion source, and an anti-bacterialagent. Stannous fluoride, and other similar compounds, would only needto be included once to achieve all of the particular benefits associatedwith its use. A preferred oral care active agent is a bleaching agent.For convenience, specific reference may be made to a bleaching agent inmany instances throughout the specification, however, any other oralcare active agent can be used in place of the bleaching agent.

The oral care active agent can comprise an anti-caries agent. Suitableanti-caries agents include any compound that has anti-caries activity.Some examples include fluoride ion sources, metal ion sources, sugaralcohols, bioglass containing compounds, and/or amino acids. Fluorideion sources can include sodium fluoride, potassium fluoride, titaniumfluoride, hydrofluoric acid, amine fluoride, sodium monofluorophosphate,stannous fluoride, and/or other suitable fluoride ion sources.

The present compositions may comprise a metal ion source that providesstannous ions, zinc ions, copper ions, or mixtures thereof. The metalion source can be a soluble or a sparingly soluble compound of stannous,zinc, or copper with inorganic or organic counter ions. Examples includethe fluoride, chloride, chlorofluoride, acetate, hexafluorozirconate,sulfate, tartrate, gluconate, citrate, malate, glycinate, pyrophosphate,metaphosphate, oxalate, phosphate, carbonate salts and oxides ofstannous, zinc, and copper. Stannous, zinc and copper ions are derivedfrom the metal ion source(s) can be found in the multi-phase oral carecomposition an effective amount to provide an oral care benefit or otherbenefits. Stannous, zinc and copper ions have been found to help in thereduction of gingivitis, plaque, sensitivity, and improved breathbenefits. An effective amount is defined as from at least about 500 ppmto about 20,000 ppm metal ion of the total composition, preferably fromabout 2,000 ppm to about 15,000 ppm. More preferably, metal ions can bepresent in an amount from about 3,000 ppm to about 13,000 ppm and evenmore preferably from about 5,000 ppm to about 10,000 ppm. This is thetotal amount of metal ions (stannous, zinc, copper and mixtures thereof)that is present in the compositions for delivery to the tooth surface.

Other metal ion sources can include minerals and/or calcium containingcompounds, which can lead to remineralization, such as, for example,sodium iodide, potassium iodide, calcium chloride, calcium lactate,calcium phosphate, hydroxyapatite, fluoroapatite, amorphous calciumphosphate, crystalline calcium phosphate, sodium bicarbonate, sodiumcarbonate, calcium carbonate, oxalic acid, dipotassium oxalate,monosodium monopotassium oxalate, casein phosphopeptides, and/or caseinphosphopeptide coated hydroxy apatite.

Sugar alcohols can include xylitol, sorbitol, erythritol, glycerin, orany other sugar alcohol that can provide an anti-caries benefit.

Bioglass containing compounds include one or more of SiO₂, CaO, Na₂O,P₂O₅, CaF₂, B₂O₃, K₂O, MgO, as described in U.S. Pat. No. 5,735,942.

Suitable amino acids include histidine, isoleucine, leucine, lysine,methionine, phenylalanine, threonine, tryptophan, valine, alanine,asparagine, aspartic acid, and glutamic acid, arginine, cysteine,glutamine, tyrosine, glycine, ornithine, proline, and serine, peptides,calcium salts of amino acids, and/or peptides.

The oral care active agent can comprise a healing agent that promotes orenhances the healing or regenerative process. Such healing agents maycomprise hyaluronic acid or salts, glucosamine or salts, allantoin,curcumin, D panthenol, niacinamide, ellagic acid, flavanoids (includingfisetin, querctin, luteolin, apigenin), vitamin E, ubiquinone, ormixtures thereof. The healing agent can also include resolvins, such aseicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well asdocosapentaenoic acid (DPA) clupanodonic acid, Resolvin D's RvD1(7S,8R,17S-trihydroxy-DHA), RvD2 (7S,16R,17S-trihydroxy-DHA), RvD3(4S,7R,17S-trihydroxy-DHA), RvD4 (4S,5,17S-trihydroxy-DHA), RvD5(7S,17S-dihydroxy-DHA), and RvD6 (4S,17S-dihydroxy-DHA) and ResolvinE's: RvE1 (5S,12R,18R-trihydroxy-EPA), 18S-Rv1(5S,12R,18S-trihydroxy-EPA), RvE2 (5S,18R-dihydroxy-EPA), and RvE3(17R,18R/S-dihydroxy-EPA), retinol, tranexamic acid, glycine, retinol,amino acids, niacinamide, and/or human growth factors.

The oral care active agent can comprise one or more probiotics selectedfrom Lactobacillus reuteri ATCC 55730; Lactobacillus salivarius strainTI12711 (LS 1); Lactobacillus paracasei ADP-1; Streptococcus salivariusK12; Bifidobacterium DN-173 010; Filtrate of L. paracasei strain(pro-t-Action™); S. Oralis KJ3, S. rattus JH145, S. uberis KJ2;Lactobacillus, reuteri Prodentis; Lactobacillus salivarius LS1;Lactobacillus paracasei; Lactobacillus paracasei ADP1; Streptococcussalivarius M18, K12 or BLIS K12 and BLIS M18; BacillusAmyloliquefaciens; Bacillus Clausii; Bacillus Coagulans; BacillusSubtilis; Bacillus subtilis: E-300; Bifidobacterium Animalis;Bifidobacterium B6; Bifidobacterium Bifidum; Bifidobacterium Breve(Bb-03); Bifidobacterium DN-173 010; Bifidobacterium GBI 30 6068;Bifidobacterium infantis; Bifidobacterium Lactis; Bifidobacterium lactisBb-12; Bifidobacterium Longum; Bifidobacterium Thermophilum;Enterococcus Faecalis; Enterococcus Faecium; Enterococcus Faecium NCIMB10415; Enterococcus LAB SF 68; Lactobacilli reuteri ATCC 55730 and ATCCPTA 5289; Lactobacilli reuteri ATCC 55730 and ATCC PTA 5289 (10:1);Lactobacillus Acidophilus; Lactobacillus acidophilus ATCC 4356 andBifidobacterium bifidum ATCC 29521; Lactobacillus acidophilus;Bifidobacterium longum; Bifidobacterium bifidum; Bifidobacterium lactis;Lactobacillus Brevis; Lactobacillus Casei (subsp. Casi); Lactobacilluscasei Shirota; Lactobacillus Confusus; Lactobacillus crispatus YIT12319; Lactobacillus Curvatus; Lactobacillus Delbrueckii Ssp. BulgaricusPXN 39; Lactobacillus Fermentum; Lactobacillus fermentum YIT 12320;Lactobacillus Gasseri; Lactobacillus gasseri YIT 12321; LactobacillusHelveticus; Lactobacillus Johnsonii; Lactobacillus Kimchii;Lactobacillus Lactis L1A; Lactobacillus Paracasei (Lpc37); Lactobacillusparacasei GMNL-33; Lactobacillus Pentosus; Lactobacillus plantarum;Lactobacillus Plantarum; Lactobacillus Protectus; Lactobacillus Reuteri;Lactobacillus reuteri ATCC 55730; Lactobacillus reuteri SD2112(ATCC55730); Lactobacillus Rhamnosus (GG); Lactobacillus rhamnosus GG;Lactobacillus rhamnosus GG; L. rhamnosus LC705; Propionibacteriumfreudenreichii ssp; shermanii JS; Lactobacillus rhamnosus L8020;Lactobacillus rhamnosus LB 21; Lactobacillus Salivarius; Lactobacillussalivarius WB21; Lactobacillus Sporogenes; Lactococcus Lactis SspDiacetylactis; Lactococcus Lactis Ssp. Lactis; Pediococcus Acidilactici;Pediococcus Pentosaceus; Saccharomyces Boulardii; SaccharomycesCerevisiae; Strep. uberis KJ2sm; Strep. oralis KJ3sm; trep. rattusJH145; Streptococcus mitis YIT 12322; Streptococcus Oralis KJ3;Streptococcus Rattus JH145; Streptococcus Salivarius (BLIS K12 or BLISM18); Streptococcus salivarius K12; Streptococcus Thermophilus;Streptococcus Uberis KJ2; Thermus thermophiles; Weissella cibaria CMS2;Weissella cibaria CMS3; and Weissella cibaria CMU.

Probiotics can be used in the multi-phase oral care compositions of thepresent invention to promote positive oral health effects, such asreduce caries and plaque, promote gum health, improve breath, andpromote whitening. The efficacy of probiotics in the multi-phase oralcare compositions can be determined by measuring one or more of thefollowing: reduction of the levels of salivary mutans streptococci;reduction of gingival crevicular fluid; reduction of periodontalpathogens (C. rectus and P. gingivitis) in subgingival plaque; decreasedcounts of yeast; decreased prevalence of oral candida; reduction of oralvolatile sulfur compound (VSC) levels; and reduction of TNF-α and IL-8production. Without being limited to theory it is believed that one ormore of the above positive oral health effects may be achieved throughthe production of bacterial toxins, which remove or reduce certain typesof bacteria in the oral cavity; further one or more of the abovepositive oral health effects may be achieved through bacterialproduction of one or more enzymes that inhibit the production of ordissolves/loosens biofilms or sticky deposits that can lead to oralhealth problems.

As the present multi-phase oral care composition can be directed tobleaching the tooth surface and removing or decreasing the stainattached thereto, a safe and effective amount may be added of at leastone anticalculus agent to the compositions as disclosed herein. Themulti-phase oral care composition may include from about 0.01% to about40%, from about 0.1% to about 25%, from about 4.5% to about 20%, or fromabout 5% to about 15%, by weight of the multi-phase oral carecomposition or any other numerical range, which is narrower, and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein, of anticalculus agent. Theanticalculus agent may also be compatible with the other components ofthe multi-phase oral care composition, in preferred embodiments thewhitening agent. The anticalculus agent may be selected from the groupconsisting of polyphosphates and salts thereof; polyamino propanesulfonic acid (AMPS) and salts thereof; polyolefin sulfonates and saltsthereof; polyvinyl phosphates and salts thereof; polyolefin phosphatesand salts thereof; diphosphonates and salts thereof; phosphonoalkanecarboxylic acid and salts thereof; polyphosphonates and salts thereof;polyvinyl phosphonates and salts thereof; polyolefin phosphonates andsalts thereof; polypeptides; and mixtures thereof, wherein the mentionedsalts can be alkali metal salts. In certain aspects anticalculus agentsused in the present multi-phase oral care composition also show astabilizing effect to the bleaching agents, such as pyrophosphates,polyphosphates, polyphophonates and mixtures thereof.

For example, the anticalculus agent may be a polyphosphate. Apolyphosphate is generally understood to comprise two or more phosphatemolecules arranged primarily in a linear configuration, although somecyclic derivatives may be present. Linear polyphosphates correspond to(X PO₃)_(n) where n is about 2 to about 125, wherein preferably n isgreater than 4, and X is for example sodium, potassium, etc. For (XPO₃)_(n) when n is at least 3 the polyphosphates can be glassy incharacter. Counter-ions for these phosphates may be the alkali metal,alkaline earth metal, ammonium, C₂-C₆ alkanolammonium and salt mixtures.Polyphosphates are generally employed as their wholly or partiallyneutralized water-soluble alkali metal salts such as potassium, sodium,ammonium salts, and mixtures thereof. The inorganic polyphosphate saltsinclude alkali metal (e.g. sodium) tripolyphosphate, tetrapolyphosphate,dialkyl metal (e.g. disodium) diacid, trialkyl metal (e.g. trisodium)monoacid, potassium hydrogen phosphate, sodium hydrogen phosphate, andalkali metal (e.g. sodium) hexametaphosphate, and mixtures thereof.Polyphosphates larger than tetrapolyphosphate usually occur as amorphousglassy materials, such as those manufactured by FMC Corporation whichare commercially known as Sodaphos (n≈6), Hexaphos (n≈13), Glass H(n≈21), and mixtures thereof. If present, the present compositions willtypically comprise from about 0.5% to about 20%, from about 4% to about15%, or preferably from about 6% to about 12%, by weight of thecomposition of polyphosphate.

The pyrophosphate salts useful in the present compositions include,alkali metal pyrophosphates, di-, tri-, and mono-potassium or sodiumpyrophosphates, dialkali metal pyrophosphate salts, tetraalkali metalpyrophosphate salts, and mixtures thereof. For example, thepyrophosphate salt is selected from the group consisting of trisodiumpyrophosphate, disodium dihydrogen pyrophosphate (Na₂H₂P₂O₇),dipotassium pyrophosphate, tetrasodium pyrophosphate (Na₄P₂O₇),tetrapotassium pyrophosphate (K₄P₂O₇), and mixtures thereof, whereintetrasodium pyrophosphate is preferred. Tetrasodium pyrophosphate may bethe anhydrous salt form or the decahydrate form, or any other speciesstable in solid form in the present compositions. The salt is in itssolid particle form, which may be its crystalline and/or amorphousstate, with the particle size of the salt preferably being small enoughto be aesthetically acceptable and readily soluble during use. The levelof pyrophosphate salt in the present compositions may be from about 1.5%to about 15%, in particular from about 2% to about 10%, and moreparticular from about 3% to about 8%, by weight of the composition.

The phosphate sources, including but are not limited to, polyphosphatesand pyrophosphates, are described in more detail in Kirk & Othmer,Encyclopedia of Chemical Technology, Fourth Edition, Volume 18,Wiley-Interscience Publishers (1996), pages 685-707.

Polyolefin phosphonates include those wherein the olefin group contains2 or more carbon atoms. Polyvinylphosphonates includepolyvinylphosphonic acid. Diphosphonates and salts thereof includeazocycloalkane-2,2-diphosphonic acids and salts thereof, ions ofazocycloalkane-2,2-diphosphonic acids and salts thereof (such as thosewhich the alkane moiety has five, six or seven carbon atoms, in whichthe nitrogen atom is unsubstituted or carries a lower alkylsubstitutent, e.g. methyl), azacyclohexane-2,2-diphosphonic acid,azacyclopentane-2,2-diphosphonic acid,N-methyl-azacyclopentane-2,3-diphosphonic acid, EHDP(ethanehydroxy-1,1,-diphosphonic acid), AHP(azacycloheptane-2,2-diphosphonic acid, a.k.a.1-azocycloheptylidene-2,2-diphosphonic acid),ethane-1-amino-1,1-diphosphonate, dichloromethane-diphosphonate, etc.Phosphonoalkane carboxylic acid or their alkali metal salts include PPTA(phosphonopropane tricarboxylic acid), PBTA(phosphonobutane-1,2,4-tricarboxylic acid), each as acid or alkali metalsalts.

In addition, antimicrobial antiplaque agents may also be present in thepresent compositions. Such agents may include, but are not limited to,triclosan, hops acids from hops extracts, such as hops alpha acids,including, humulone, adhumulone, cohumulone, posthumulone, prehumulon,and combinations thereof, or hops beta acids, including, lupulone,adlupulone, colupulone, and combinations thereof,5-chloro-2-(2,4-dichlorophenoxy)-phenol, as described in The MerckIndex, 11th ed. (1989), pp. 1529 (entry no. 9573) in U.S. Pat. No.3,506,720, and in European Patent Application No. 0,251,591;chlorhexidine (Merck Index, no. 2090), alexidine (Merck Index, no. 222;hexetidine (Merck Index, no. 4624); sanguinarine (Merck Index, no.8320); benzalkonium chloride (Merck Index, no. 1066); salicylanilide(Merck Index, no. 8299); domiphen bromide (Merck Index, no. 3411);cetylpyridinium chloride (CPC) (Merck Index, no. 2024;tetradecylpyridinium chloride (TPC); N-tetradecyl-4-ethylpyridiniumchloride (TDEPC); octenidine; delmopinol, octapinol, and otherpiperidino derivatives; In addition there may be effective antimicrobialamounts of essential oils and combinations thereof for example citral,geranial, and combinations of menthol, eucalyptol, thymol and methylsalicylate; antimicrobial metals and salts thereof for example thoseproviding zinc ions, stannous ions, copper ions, and/or mixturesthereof; bisbiguanides, or phenolics; antibiotics such as augmentin,amoxicillin, tetracycline, doxycycline, minocycline, and metronidazole;and analogs and salts of the above antimicrobial antiplaque agentsand/or anti-fungals such as those for the treatment of Candida albicans.If present, these agents generally are present in a safe and effectiveamount for example from about 0.1% to about 5% by weight of the presentcompositions.

The oral care active agent can comprise one or more anti-inflammatoryagents. Such anti-inflammatory agents may include, but are not limitedto, non-steroidal anti-inflammatory agents such as aspirin, ketorolac,flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, ketoprofen,piroxicam and meclofenamic acid, COX-2 inhibitors such as valdecoxib,celecoxib and rofecoxib, and mixtures thereof. If present, theanti-inflammatory agents generally comprise from about 0.001% to about5% by weight of the compositions.

The oral care active agent can comprise one or more minerals. Theminerals may improve the teeth and the tooth surface and thus can beincluded with the compositions as disclosed herein. Suitable mineralsinclude e.g. calcium, phosphorus, fluoride, zinc, manganese, potassiumand mixtures thereof. These minerals are e.g. disclosed in Drug Factsand Comparisons (loose leaf drug information service), Wolters KluerCompany, St. Louis, Mo., ©1997, pp 10-17.

Suitable bleaching agents can comprise agents that provide bleachingeffects, stain bleaching effects, stain removal effects, stain colorchange effects or any other effect, which change, or brighten toothcolor. For example, bleaching agents can comprise a source of peroxideradicals. In addition, bleaching agents may include peroxides, metalchlorites, perborates, percarbonates, peroxyacids, persulfates,compounds that form the preceding compounds in situ, and combinationsthereof. Examples of peroxide compounds include hydrogen peroxide, ureaperoxide, calcium peroxide, carbamide peroxide, and mixtures thereof. Incertain embodiments, the bleaching agent may be hydrogen peroxide(H₂O₂). Suitable metal chlorites include calcium chlorite, bariumchlorite, magnesium chlorite, lithium chlorite, sodium chlorite,potassium chlorite, and mixtures thereof. Additional bleach agents alsoinclude hypochlorite (such as metal hypochlorite) and chlorine dioxide.Persulfates include salts of peroxymonosulfate, peroxydisulfate andmixtures thereof. The oral care active agent, such as a bleaching agent,can be introduced into the multi-phase oral care composition oroil-in-water emulsion as an aqueous solution, as a solid, or as aliquid. Preferably, the active agent is introduced into the multi-phaseoral care composition as an aqueous solution.

The multi-phase oral care composition or high internal phase emulsionpreferably jammed oil-in-water emulsion can comprise from about 0.01% toabout 10%, from about 0.05% to about 5%, from about 0.01% to about 1%,0.01% to less than 1%, from about 1% to about 10%, greater than 1% toabout 10%, from about 3% to about 20%, or preferably from about 0.5% toabout 5%, by weight of the multi-phase oral care composition or jammedoil-in-water emulsion, of the active agent, such as a bleaching agent.

The aqueous phase of can comprise from about 5% to about 67%, from about10% to about 50%, or preferably, from about 15% to about 50%, by weightof the aqueous phase, of the active agent, such as a bleaching agent

Surprisingly, bleaching agents can be significantly effective when usedeven at the low levels in the multi-phase oral care compositions asdisclosed herein, which may be in the form of jammed oil-in-wateremulsions.

The multi-phase oral care compositions or jammed oil-in-water emulsions,as described herein, can deliver a high ratio of the concentration inweight percent of bleaching agent present in the aqueous phase to theconcentration in weight percent of bleaching agent present in theoverall multi-phase oral care composition, as they have a highconcentration in weight percent of bleaching agent present in theaqueous phase combined with a relatively low concentration in weightpercent of bleaching agent present in the overall multi-phase oral carecomposition. Without being bound by theory, this surprising combinationof seemingly contradictory parameters in the present invention deliversthe bleaching agent to the tooth surface with a high driving force evenwhen the overall concentration or amount of bleaching agent delivered tothe tooth surface is low. As a result, the high driving force delivers asurprisingly high level of bleaching efficacy and/or bleaching speed;while the low overall concentration or low amount of bleaching agentdelivered to the tooth surface may help reduce tooth sensitivity

The ratio of the concentration in weight percent of bleaching agentpresent in the aqueous phase to the concentration in weight percent ofbleaching agent present in the overall multi-phase oral care compositionmay be from about 67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500,2000, 1750, 1160, 1000, 875, 700, 580, 500, 430, 400, 380, 350, 200,175, 111, 110, 105, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 toabout 67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500, 2000, 1750,1160, 1000, 875, 700, 580, 500, 430, 400, 380, 350, 200, 175, 111, 110,105, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

The bleaching agents of the present invention may be stabilized againstdegradation by the shielding effect of the hydrophobic phase. Forexample, after 180 days of storage at 30° C. following formulation,multi-phase oral care compositions of the present invention can compriseat least about 10% of the initial amount of hydrogen peroxide they wereformulated with. Additionally, at least about 25% of the initial amountof hydrogen peroxide, at least about 50% of the initial amount ofhydrogen peroxide, or at least about 75% of the initial amount ofhydrogen peroxide may be present after 180 days storage of thecomposition at 30° C.

The multi-phase oral care compositions can comprise at least about 10%,20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100%of the initial level of bleaching agent at temperatures (for example −7°C., 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or 60° C.) andconditions that the multi-phase oral care composition may be exposed toduring manufacture, filling, shipping, or storage (for example 1 day, 2days, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months,18 months, or 24 months) prior to use by the consumer.

The stabilizing agent can be present in a multi-phase oral carecomposition of the present invention in an amount from about 0.0000001%to about 0.1%, from about 0.000001% to about 0.01%, up to about 0.1%, orpreferably up to about 1%, by weight of the multi-phase oral carecomposition, jammed oil-in-water emulsion, or the aqueous phase.

The multi-phase oral care compositions or jammed oil-in-water emulsions,as described herein, may comprise a stabilizing agent for the bleachingagent. The bleaching agent may be further stabilized against degradationby the multi-phase oral care composition. Stabilizing agents may beadded to the multi-phase oral care composition, such as in the aqueousphase. Suitable stabilizing agents include for example ortho-phosphoricacid, phosphate(s), such as sodium hydrogen phosphate, pyrophosphate(s),organophosphonate(s), Ethylenediaminetetraacetic acid,Ethylenediamine-N,N′-diacetic acid, Ethylenediamine-N,N′-disuccinicacid, potassium stannate, sodium stannate, tin salts, zinc salts,salicylic acid, 1-Hydroxyethylidene-1,1-diphosphonic acid, andcombinations thereof. Suitable stabilizers can also show additional oralcare effects, such as anti-tartar effect, produced by pyrophosphate(s)or organophosphonate(s).

A stabilizing agent may also include chelants. The chelant may be acopper, iron and/or manganese chelants, or a mixture thereof. Suitablechelants may be selected from: diethylene triamine pentaacetate,diethylene triamine penta(methyl phosphonic acid), ethylenediamine-N′N′-disuccinic acid, ethylene diamine tetraacetate, ethylenediamine tetra(methylene phosphonic acid), hydroxyethane di(methylenephosphonic acid), and any combination thereof. A suitable chelant may beselected from ethylene diamine-N′N′-disuccinic acid (EDDS),hydroxyethane diphosphonic acid (HEDP) or mixtures thereof. Thestabilizer may comprise ethylene diamine-N′N′-disuccinic acid or saltthereof. The ethylene diamine-N′N′-disuccinic acid may be in S,Senantiomeric form. The stabilizer may comprise4,5-dihydroxy-m-benzenedisulfonic acid disodium salt, glutamicacid-N,N-diacetic acid (GLDA) and/or salts thereof,2-hydroxypyridine-1-oxide, Trilon P™ available from BASF, Ludwigshafen,Germany. Suitable chelants may also be calcium carbonate crystal growthinhibitors. Suitable calcium carbonate crystal growth inhibitors may beselected from the group consisting of: 1-hydroxyethanediphosphonic acid(HEDP) and salts thereof; N,N-dicarboxymethyl-2-aminopentane-1,5-dioicacid and salts thereof; 2-phosphonobutane-1,2,4-tricarboxylic acid andsalts thereof; and any combination thereof.

The stabilizer may comprise a calcium carbonate crystal growthinhibitor, such as 1-hydroxyethanediphosphonic acid (HEDP);N,N-dicarboxymethyl-2-aminopentane-1,5-dioic acid;2-phosphonobutane-1,2,4-tricarboxylic acid; and salts thereof; and anycombination thereof.

The stabilizer may comprise a hydroxamate chelant. By ‘hydroxamate’ weherein mean hydroxamic acid or a corresponding salt, for example cocohydroxamic acid (Axis House RK 853).

Emulsifiers

The multi-phase oral care composition or high internal phase emulsionpreferably a jammed oil-in-water emulsion, as described herein,comprises one or more emulsifiers. Depending on the design of themulti-phase oral care composition, the hydrophobic phase can haveemulsifying properties. Thus, the emulsifier and the hydrophobic phasecan comprise the same compound.

The multi-phase oral care composition or high internal phase emulsionpreferably a jammed oil-in-water emulsion, as described herein, cancomprise from about 0.001% to about 20%, from about 0.01% to about 10%,up to about 10%, up to about 5%, or preferably from about 0.1% to about10%, by weight of the multi-phase oral care composition or jammedoil-in-water emulsion, of the emulsifier.

Classes of surfactants useful as emulsifiers include nonionic, anionic,cationic, amphoteric, polymeric, synthetic emulsifiers, and mixturesthereof. Many suitable nonionic and amphoteric surfactants are disclosedby U.S. Pat. Nos. 3,988,433; 4,051,234, and many suitable nonionicsurfactants are also disclosed by U.S. Pat. No. 3,959,458.

The emulsifier can comprise a polysorbate, an alkyl sulfate, Lipowax® D,or combinations thereof. Suitable polysorbate compounds include,polysorbate 20, 40, 60, 80, or combinations thereof, such as Tween® 20,40, 60, 80, or combinations thereof.

The emulsifier can comprise natural emulsifiers, such as acacia,gelatin, lecithin and cholesterol; finely dispersed solids, such ascolloidal clays, bentonite, veegum (magnesium aluminum silicate; andsynthetic emulsifiers, such as salts of fatty acids, sulfates such assorbitan trioleate, sorbitan tristearate, sucrose distearate, propyleneglycol monostearate, glycerol monostearate, propylene glycolmonolaurate, sorbitan monostearate, sorbitan monolaurate,polyoxyethylene-4-lauryl ether, sodium lauryl sulfate, sulfonates suchas dioctyl sosium sulfosuccinate, glyceryl esters, polyoxyethyleneglycol esters and ethers, diethylene glycol monostearate, PEG 200distearate, and sorbitan fatty acid esters, such as sorbitanmonopalmitate, and their polyoxyethylene derivatives, polyoxyethyleneglycol esters such as the monostearate, Polysorbate 80 (ethoxylatedsorbitan monooleate) (supplied by Spectrum, etc.); and combinationsthereof.

The emulsifier can be a surfactant that is non-reactive with a bleachingagent. For example, surfactants that are non-reactive with a bleachingagent may be substantially free of hydroxy groups, nitrogen groups andlinkages, double or triple covalent bonds between adjacent carbon atoms,metals such as Zn, etc., or combinations thereof.

The multi-phase oral care compositions may be substantially free ofingredients, for example reactive emulsifiers, that at temperatures (forexample −7° C., 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or 60°C.) and conditions that the multi-phase oral care composition may beexposed to during manufacture, filling, shipping, or storage (forexample 1 day, 2 days, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6months, 12 months, 18 months, or 24 months) prior to use by theconsumer, 1) may compromise the efficacy, comfort, usage experience,concentration of actives or bleaching agents at the tooth surface overtime, active or bleaching efficiency, or compatibility betweeningredients, or 2) may react with other ingredients or degrade otheringredients or may cause foam or pressure to build up in the package orcontainer in which the multi-phase oral care composition is stored.“Substantially free of a reactive emulsifier” as used herein means thatthe composition comprises less than 0.001% by weight of a reactiveemulsifier.

The emulsifier may be a non-ionic surfactant. Nonionic surfactantsinclude polyoxyethylene sorbitan fatty acid esters, such as, materialssold under the trademark Tween. The number following the‘polyoxyethylene’ part in the following section refers to the totalnumber of oxyethylene —(CH₂CH₂O)— groups found in the molecule. Thenumber following the ‘polysorbate’ part is related to the type of fattyacid associated with the polyoxyethylene sorbitan part of the molecule.Monolaurate is indicated by 20, monopalmitate is indicated by 40,monostearate by 60, and monooleate by 80. Examples of such materials arepolyoxyethylene (20) sorbitan monolaurate (Tween 20), polyoxyethylene(20) sorbitan monopalmitate (Tween 40), polyoxyethylene (20) sorbitanmonostearate (Tween 60), polyoxyethylene (4) sorbitan monostearate(Tween 61), polyoxyethylene (20) sorbitan tristearate (Tween 65),polyoxyethylene (20) sorbitan monooleate (Tween 80), polyoxyethylene (5)sorbitan monooleate (Tween 81), and polyoxyethlene (20) sorbitantrioleate (Tween 85), and mixtures thereof. Polyoxyethylene fatty acidesters are also suitable and examples include those materials sold underthe trademark Myrj such as polyoxyethylene (8) stearate (Myrj 45) andpolyoxyethylene (40) stearate (Myrj 52), and mixtures thereof. Furthernonionics include, polyoxyethylene polyoxypropylene block polymers, suchas poloxamers and Pluronics.

Another suitable class of non-ionic surfactants that can be used in theemulsifier are polyoxyethylene fatty ethers, such as, the materials soldunder the trademark Brij. Examples of such materials are polyoxyethylene(4) lauryl ether (Brij 30), polyoxyethylene (23) lauryl ether (Brij 35),polyoxyethylene (2) cetyl ether (Brij 52), polyoxyethylene (10) cetylether (Brij 56), polyoxyethylene (20) cetyl ether (Brij 58),polyoxyethylene (2) stearyl ether (Brij 72), polyoxyethylene (10)stearyl ether (Brij 76), polyoxyethylene (20) stearyl ether (Brij 78),polyoxyethylne (2) oleyl ether (Brij 93), polyoxyethylene (10) oleylether, and polyoxyethylene (20) oleyl ether (Brij 99), and mixturesthereof.

A portion of a non-ionic surfactant may be substituted with a lipophilicsurfactant, such as, sorbitan fatty acid esters such as the materialssold under the trademark Arlacel. Suitable lipophilic surfactantsinclude sorbitan monolaurate (Arlacel 20), sorbitan monopalmitate(Arlacel 40), sorbitan monostearate (Aracel 60), sorbitan monooleate(Arlacel 80), sorbitan sesquioleate (Arlacel 83), and sorbitan trioleate(Arlacel 85), and mixtures thereof. Typically, from about 2% to about90% of the level of the nonionic surfactant may be substituted by alipophilic surfactant, or from about 25% to about 50%.

Each emulsifier and/or blends of multiple emulsifiers can have ahydrophilic-lipophilic balance (HLB) value. An emulsifier that islipophilic in character is assigned a low HLB number (below about 9),and one that is hydrophilic is assigned a high HLB number (above about11). In certain embodiments, the skilled formulator will recognize theimportance of selecting an emulsifier (or blend of multiple emulsifiers)with a suitable balance of hydrophilic and lipophilic properties toencourage the formation of a high internal phase emulsion or preferablya jammed emulsion. The HLB is calculated according to the procedurespecified previously. Information on emulsifiers and HLB values can befound in 1) “Emulsion science and technology” edited by Tharwat F.Tadros, Wiley VCH, ISBN: 978-3-527-32525-2, 2) “Classification ofsurface-active agents by HLB” by W. C. Griffin of the Atlas PowderCompany in the Journal of Cosmetic Chemists 1949, 3) “Calculation of HLBof non-ionic surfactants” by W. C. Griffin in the Journal of CosmeticChemists 1954, 4) “Interfacial phenomena”, Chapter 8 “Disperse systemsand adhesion” by J. T. Davies and E. K. Rideal Academic Press, New York,1963, 5) “A quantitative kinetic theory of emulsion type I, physicalchemistry of the emulsifying agent” by J. T. Davies J. H. Schulman(Ed.), Proceedings of the 2nd International Congress on SurfaceActivity, 1, Academic Press, New York (1957), 6) “Span and Tween”brochure 08/10 D1005/1 by Croda Europe Ltd. England, 7) “Food enrichmentwith Omega-3 fatty acids”, Chapter 5 “Stabilization of omega-3 oils andenriched foods using emulsifiers” by C. Genot, T.-H. Kabri and A.Meynier, France, Woodhead Publishing, and 8) “Health Care ProdoctGuide—North America”, brochure “Pharmaceuticals, Dermatology, Deliveringyour solution, Animal Health, Nutraceuticals” by Croda. The emulsifiersand blends of multiple emulsifiers along with their HLB values specifiedin these documents are incorporated herein by reference.

An emulsifier that tends to form a water-in-oil emulsion and anemulsifier that forms an oil-in-water emulsion may be blended to achievean HLB suitable for an oil-in-water emulsion. The average HLB number ofthe blend may be calculated from additivity:HLB of blend=(a)*HLB₁+(b)*HLB₂

Wherein a and b are the weight fractions of the two emulsifiers withHLB₁ and HLB₂.

For example, to determine the HLB value of a blend comprising 70% ofTWEEN 80 (HLB=15) and 30% Of SPAN 80 (HLB=4.3), the calculation wouldbe:

The contribution from TWEEN 80 is 70%×15.0=10.5

The contribution from SPAN 80 is 30%×4.3=1.3

Thus, the HLB of blend is 11.8 (i.e. 10.5+1.3)

The HLB values of various emulsifiers and/or blends of multipleemulsifiers can be from about are from about 0 to about 60, above 11,from about 11 to about 60, from about 11 to about 40, preferably fromabout 11 to about 20, or more preferred from about 16 to about 18, orcombinations thereof; or from about 20 to about 40, or from about 30 toabout 40.

The emulsifier or blend of multiple emulsifiers can be hydrophilic,miscible with water, immiscible with mineral oil, or combinationsthereof.

Each emulsifier can comprise at least one hydrophobic tail group and atleast one hydrophilic head group. There can be from about 6 to about 20,from about 8 to about 16, or from about 10 to 14 carbon atoms in fromabout 1 to about 4, from about 1 to about 3, or from about 1 to about 2hydrophobic tails, or in 1 hydrophobic tail. Each hydrophobic tail canhave up to about 4, up to about 3, or up to about 1 branch, or 0branches. Each hydrophobic tail can have up to about 3, up to about 2,up to about 1, or 0 alkene functional groups (or carbon-carbon doublebonds). The hydrophilic head group of each emulsifier molecule cancomprise from about PEG-4 to about PEG-40, from about PEG-8 to aboutPEG-30, or preferably from about PEG-16 to about PEG-24 attached tosorbitan. The emulsifier can comprise from about 4 to about 60, fromabout 8 to about 30, from about 16 to about 34 of moles of ethyleneoxide in each emulsifier molecule.

The emulsifier or blend of multiple emulsifiers can comprise PEG-20sorbitan monolaurate (Tween 20), PEG-20 sorbitan monooleate (Tween 80),and/or sodium lauryl sulfate. Preferably, the emulsifier can comprisePEG-20 sorbitan monolaurate.

The emulsifier (and HLB) may comprise one or more of the following list,and blends of multiple emulsifiers may comprise blends of these in anycombination thereof: Span 20 (HLB of 8.6), Span 40 (6.7), Span 60 (4.7),Span 80 (4.3), Span 83 (3.7), Span 85 (1.8), Span 120 (4.7), Tween 20(16.7), Tween 21 (13.3), Tween 40 (15.6), Tween 60 (14.9), Tween 61(9.6), Tween 65 (10.5), and Tween 80 (15).

Other Optional Components

The multi-phase oral care composition as disclosed herein may compriseadditional optional ingredients, and which will be described below infurther detail.

The multi-phase oral care compositions herein may comprise a safe andeffective amount of a thickening agent, viscosity modifier orparticulate fillers. A thickening agent may further provide acceptablerheology of the composition. The viscosity modifier may further functionto inhibit settling and separation of components or control settling ina manner that facilitates re-dispersion and may control flow propertiesof the composition. In addition, a thickening agent or viscositymodifier may facilitate use of the present compositions with suitableapplications devices, such as strips, films or dental trays byincreasing the retention onto the surfaces of the application devices.The thickening agent, as described herein, may also serve as anadhesive. When present a thickening agent, viscosity modifier, orparticulate filler may be present from about 0.1% to about 50%, fromabout 1% to about 25%, or from about 1% to about 10%, by weight of themulti-phase oral care composition.

Suitable thickening agents, viscosity modifiers, or particulate fillersthat can be used herein include organo modified clays, silicas,synthetic polymers such as crosslinked siloxanes, cellulose derivatives(e.g. methylcellulose, carboxymethylcellulose, hydroxyethylcellulose,hydroxypropyl-cellulose, hydroxy-propylmethylcellulose, etc.), carbomerpolymers (e.g. crosslinked polyacrylic acid copolymer or homopolymer andcopolymers of acrylic acid cross linked with a polyalkenyl polyether),natural and synthetic gums, karaya gum, guar gum, gelatin, algin, sodiumalginate, tragacanth, chitosan, polyethylene oxide, acrylamide polymers,polyacrylic acid, polyvinyl alcohol, polyamines, polyquarternarycompounds, ethylene oxide polymers, polyvinylpyrrolidone, cationicpolyacrylamide polymers, waxes (which includes paraffin wax andmicrocrystalline waxes), polyethylene, fumed silica, polymethacrylates,olefin copolymers, hydrogenated styrene-diene copolymers, styrenepolyesters, rubber, polyvinylchloride, nylon, fluorocarbon, polyurethaneprepolymer, polyethylene, polystyrene, alkylated polystyrene,polypropylene, cellulosic resins, acrylic resins, elastomers,poly(n-butyl vinyl ether), poly(styrene-co-maleic anhydride), poly(alkylfumarate co-vinyl acetate), poly(t-butyl styrene), and mixtures thereof.

Examples of polyethylene include A-C 1702 or A-C 6702 made by HoneywellCorp. (Morristown, N.J.), with a penetration value of about 98.5 andabout 90.0, respectively, under ASTM D1321; polyethylene Performaleneseries from Baker Hughes; this includes polyethylene Performalene 400from Baker Hughes Inc. (Houston, Tex.). Examples of microcrystalline waxinclude the Multiwax series from Sonneborn (Parsippany, N.J.), Crompton(Witco); these include Multiwax 835, Multiwax 440, Multiwax 180, andmixtures thereof.

Examples of polymethacyrlates include, for example,polyacrylate-co-methacrylate, polymethacrylate-co-styrene, orcombinations thereof. Examples of elastomers include, for instance,hydrogenated styrene-co-butadiene, hydrogenated styrene-co-isoprene,ethylene-ethylene-propylene polymer, ethylene-propylene polymer,styrene-ethylene-ethylene-propylene-styrene polymer or combinationsthereof. An example of a rubber includes hydrogenated polyisoprene.Other examples of viscosity modifiers can be found in “Chemistry andTechnology of Lubricants,” Chapman and Hall (2^(nd) Ed. 1997).

Suitable carbomers comprises the class of homopolymers of acrylic acidcrosslinked with an alkyl ether of pentaerythritol or an alkyl ether ofsucrose. Carbomers are commercially available from B.F. Goodrich as theCarbopol® series, such as Carbopol 934, 940, 941, 956, and mixturesthereof. Homopolymers of polyacrylic acid are described, for example, inU.S. Pat. No. 2,798,053. Other examples of homopolymers which are usefulinclude Ultrez 10, ETD 2050, and 974P polymers, which are available fromThe B.F. Goodrich Company (Greenville, S.C.). Such polymers includehomopolymers of unsaturated, polymerizable carboxylic monomers such asacrylic acid, methacrylic acid, maleic acid, itaconic acid, maleicanhydride, and the like.

Coolants, desensitizing agents and numbing agents can be used asoptional ingredients in compositions of the present invention, such asat a level of from about 0.001% to about 10%, or preferably from about0.1% to about 1%, by weight of the composition. Coolants, desensitizingagents and numbing agents may decrease potential negative perceptions,such as tingling, burning etc. . . . Coolant can be any of a widevariety of materials. Included among such materials are carboxamides,menthol, ketals, diols, and mixtures thereof. Optional coolants in thepresent compositions may be the paramenthan carboxyamide agents such asN-ethyl-p-menthan-3-carboxamide (known as “WS-3”),N,2,3-trimethyl-2-isopropylbutanamide (known as “WS-23”), menthol,3-1-menthoxypropane-1,2-diol (known as TK-10), menthone glycerol acetal(known as MGA) menthyl lactate (known as Frescolat®), and mixturesthereof. The terms menthol and menthyl as used herein include dextro-and levorotatory isomers of these compounds and racemic mixturesthereof. Desensitizing or Anti-pain agent may include, but are notlimited to, strontium chloride, potassium nitrate, oxalate salts oracids, natural herbs such as gall nut, Asarum, Cubebin, Galanga,scutellaria, Liangmianzhen, Baizhi, etc. Suitable numbing agents includebenzocaine, lidocaine, clove bud oil, and ethanol.

In addition, the compositions as disclosed herein may optionallycomprise a safe and effective amount of a flavoring agent. Suitableflavoring agents include oil of wintergreen, oil of peppermint, oil ofspearmint, clove bud oil, menthol, anethole, methyl salicylate,eucalyptol, 1-menthyl acetate, sage, eugenol, parsley oil, oxanone,alpha-irisone, marjoram, lemon, orange, propenyl guaethol, cinnamon,vanillin, thymol, linalool, cinnamaldehyde glycerol acetal (known asCGA), and mixtures thereof. If present the flavoring agents aregenerally used at levels of from about 0.01% to about 30%, preferablyfrom about 0.5% to about 20%, more particular from about 1.5% to about15%, by weight of the composition.

In addition, the present compositions may optionally comprise sweeteningagents including sucralose, sucrose, glucose, saccharin, dextrose,levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol,saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcones,acesulfame and cyclamate salts, especially sodium cyclamate and sodiumsaccharin, and mixtures thereof. If present, the composition containsfrom about 0.1% to about 10% of these agents, or preferably from about0.1% to about 1%, by weight of the composition.

In addition, dyes, pigments, colorants, and mixtures thereof mayoptionally be included in the present composition to give thecompositions herein colored appearance. An advantage of adding pigmentsand/or colorants to the compositions herein is that it will allow thepatient to see if the composition covers their teeth evenly andcompletely, since coverage is easier to see with a colored composition.In addition, the colorant may provide color similar to the color ofbleached teeth. Colorants useful herein are stable with the bleach agentand are those recognized as safe. The levels of dye, pigments andcolorants that are optionally used herein are in the range of about0.05% to about 20%, preferably from about 0.10% to about 15% and morepreferably from about 0.25% to about 5% by weight of the composition.

Multi-Phase Compositions Comprising a Peroxide Compound

For multi-phase oral care compositions that comprise peroxide, it hasbeen surprisingly found that the standard deviation of the peroxideconcentration of a multi-phase oral care composition smeared ontoperoxide test strips is a factor to decrease oral/topical irritationand/or tooth-sensitivity during use. Each peroxide test strip has tworeaction-zones that change color (driving the R value intensity lower)in areas or spots that are contacted with peroxide. Thus, without beingbound by theory, peroxide test strips may conveniently be used as aproxy for oral/topical/tooth surfaces to identify spots of high peroxideconcentration that may lead to oral/topical irritation and/ortooth-sensitivity.

Furthermore, since contact with peroxide drives the R value intensitylower in the reaction-zones, the mean R value intensity of peroxide teststrips smeared with the multi-phase oral care composition subtractedfrom the mean baseline R value intensity of untreated peroxide teststrips may conveniently be used as a measure of the mean peroxideconcentration. Multi-phase oral care compositions that have large spotsof high peroxide concentration when the multi-phase oral carecomposition is smeared on peroxide test strips may also have large spotsof high peroxide concentration when the multi-phase oral carecomposition is applied to oral/topical/tooth surfaces—this in turn maylead to oral/topical irritation and/or tooth-sensitivity. In contrast,multi-phase oral care compositions that have only small spots of highperoxide concentration when the multi-phase oral care composition issmeared onto peroxide test strips may also have only small spots of highperoxide concentration when the multi-phase oral care composition isapplied to oral/topical/tooth surfaces—this in turn may lead to loworal/topical irritation and/or tooth-sensitivity. The spots of peroxideconcentration when the multi-phase oral care composition is smeared ontoperoxide test strips can be quantified by the standard deviation of theperoxide concentration on the test strips measured using the methodspecified herein. Multi-phase oral care compositions that have largespots of high peroxide concentration when the multi-phase oral carecomposition is smeared onto peroxide test strips have a high standarddeviation of the peroxide concentration on the test strips. In contrast,multi-phase oral care compositions that have only small spots of highperoxide concentration when the multi-phase oral care composition issmeared onto peroxide test strips have a low standard deviation of theperoxide concentration on the test strips.

Furthermore, multi-phase oral care compositions with large droplets ofthe aqueous phase may cause large spots of high peroxide concentrationwhen the multi-phase oral care composition is smeared onto peroxide teststrips—this in turn may lead to a high standard deviation of theperoxide concentration on the test strips. In contrast, multi-phase oralcare compositions that have little or no large droplets of the aqueousphase may cause only small spots of high peroxide concentration when themulti-phase oral care composition is smeared onto peroxide teststrips—this in turn may lead to a low standard deviation of the peroxideconcentration on the test strips.

The standard deviation of the peroxide concentration of a multi-phaseoral care composition smeared onto peroxide test strips measured usingthe method specified herein can be up to about 50, up to about 25, up toabout 10, from about 5 to about 15, or preferably from about 1 to about10.

For multi-phase oral care compositions that comprise peroxide, it hassurprisingly been found that the mean peroxide concentration of amulti-phase oral care composition smeared onto peroxide test strips is afactor to deliver bleaching efficacy. Without being bound by theory, ifthe mean peroxide concentration of a multi-phase oral care compositionsmeared onto peroxide test strips is low, the mean peroxideconcentration delivered to the tooth surface during use may also be low,which could lead to low bleaching effectiveness. In contrast, if themean peroxide concentration of a multi-phase oral care compositionsmeared onto peroxide test strips is high, the mean peroxideconcentration delivered to the tooth surface during use may also behigh, which could lead to high bleaching effectiveness.

The mean peroxide concentration of a multi-phase oral care compositionsmeared onto peroxide test strips measured using the method specifiedherein may be from about 10 to about 225, from about 25 to about 200, orpreferably from about 40 to about 100.

In contrast, if the ratio of the mean peroxide concentration of amulti-phase oral care composition smeared onto peroxide test strips tothe standard deviation of the peroxide concentration of a multi-phaseoral care composition smeared onto peroxide test strips is low, thecomposition may deliver low efficacy combined with high oral/topicalirritation and/or tooth-sensitivity during use. The ratio of the meanperoxide concentration of a multi-phase oral care composition smearedonto peroxide test strips measured using the method specified herein tothe standard deviation of the peroxide concentration of a multi-phaseoral care composition smeared onto peroxide test strips measured usingthe method specified herein may be no less than about 0.25, 0.5, 1, 1.5,2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50 or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein. The ratio of the mean peroxide concentration of amulti-phase oral care composition smeared onto peroxide test stripsmeasured using the method specified herein to the standard deviation ofthe peroxide concentration of a multi-phase oral care compositionsmeared onto peroxide test strips measured using the method specifiedherein may be no less than about 0.5, preferably no less than about 1,more preferably no less than about 2, and most preferably no less thanabout 3.5, or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

It has surprisingly been found that the Brookfield Viscosity of themulti-phase oral care compositions of the present invention impacts themean peroxide concentration of a multi-phase oral care compositionsmeared onto peroxide test strips measured according to the methodspecified herein. Specifically, it has been surprisingly found thatmulti-phase oral care compositions of the present invention with a lowerBrookfield Viscosity deliver a higher mean peroxide concentration of themulti-phase oral care compositions smeared onto peroxide test stripsmeasured according to the method specified herein.

The components of the aqueous phase and hydrophobic phase are chosen toallow for the release of the oral care active, which may be a bleachingagent dissolved in the aqueous phase, readily from the composition.

Without being bound by theory it is believed that when the presentinvention, which may be in the form of a jammed oil-in-water emulsion,is brought into contact with a tooth surface, the aqueous phase and thecomponents of the aqueous phase may migrate to the tooth surface. Thepossible net effect is that the active effect, which may be a toothwhitening effect, is started only after contact with the tooth surfaceto be treated. That means, the active which may be a bleaching agent maybe protected against environmental influence and thereby stabilized bythe hydrophobic phase of the multi-phase oral care composition untiluse. Thereby, the active effect may be applied to the tooth surface andthe active agent, e.g. the bleaching agent may be potentially shieldedagainst the oral environment during use. Thereby the efficacy of awhitening multi-phase oral care composition may be enhanced and/oraccelerated.

Without further being bound by theory, the present invention may improvethe delivery of the whitening agent to the tooth surface and thus thewhitening performance due to the partial hydrophobic and partialhydrophilic nature of the composition. Due to the driving forceresulting therefrom the active agent, which may be a bleaching agentpresent in the aqueous phase, may be driven towards the tooth surface.Thereby increased speed of whitening and increased efficacy of thebleaching agent may be achieved, even though surprisingly low totallevels of the bleaching agent can be used. Certain embodiments of thepresent invention, at a given total overall concentration, such as 0.1%,0.5%, 1%, 2,%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%, by weight or below ofa bleaching agent, delivers a surprisingly high level of whiteningefficacy, may require fewer applications to get the same degree ofwhitening, or may require a lower gel load (milligrams of gel per unitarea) to get the same degree of whitening.

In addition, retention of the multi-phase oral care composition on thetooth surfaces may be improved as the hydrophobic phase resists salivarydilution and salivary enzymes which can decompose the peroxide. Evenfurthermore, the hydrophobic phase likely does not dehydrate the teethcreating an outward flux of water created by many hydrophiliccompositions containing hydrophilic adhesives such as polycarboxylicacid. Since the hydrophobic phase likely does not dehydrate the teeth itmay result in a surprisingly low level of tooth sensitivity even whiledelivering a surprisingly high level of whitening efficacy.

In addition, the hydrophobic phase may provide further advantages. Forexample, the hydrophobic phase represents a stable matrix foringredients which can be soluble in the hydrophobic phase. For example,many oil-soluble active agents or flavor ingredients usually used inoral compositions may be soluble in the hydrophobic phase. That meansthe flavor ingredients may be protected from any influence of the activeagent, for example the bleaching agent, in the oral composition. Inaddition, during use of the oral composition at the tooth surface atleast part of the hydrophobic phase may be located—without being boundby theory—towards the soft oral tissues, such as the mucosa, therebypresenting the ingredients which can be present in the hydrophobicphase, such as flavor compounds, to the oral cavity. In addition, thehydrophobic phase may shield the active agent, such as the bleachingagent against any influence from the oral cavity, such as dilution bysaliva. The shielding effect may also apply to the tooth surface(s)themselves, wherein the hydrophobic phase may provide greater hydrationof the teeth surfaces.

The multi-phase oral care compositions of the present invention may bein the form of a liquid, viscous liquid, gel, semisolid, solid,particulate, powder, viscoelastic liquid, viscoelastic gel, sol,viscoelastic solid, or any combination thereof.

Without being bound by theory, macroscopic separation of one or more ofthe components of the multi-phase oral care composition at temperatures(for example −7° C., 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or60° C.) and conditions that the multi-phase oral care composition may beexposed to during manufacture, filling, shipping, or storage (forexample 1 day, 2 days, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6months, 12 months, 18 months, or 24 months) prior to use by the consumermay compromise the efficacy, comfort, usage experience, concentration ofactives or bleaching agents at the tooth surface over time, active orbleaching efficiency, or compatibility between ingredients. Themulti-phase oral care composition can be considered stable if there isno more than about 1%, 2%, or 5%, by total volume of the multi-phaseoral care composition, macroscopic separation for at least 2 days or 7days while being stored at 23° C., 40° C., and/or 60° C., as measuredaccording to the method described herein.

For example, compositions that exhibit macroscopic separation of thebleaching agent or phases that contain a bleaching agent prior to use bythe consumer may cause the concentration of bleaching agent to changefrom one dose to the other, and/or over time. This can compromise theefficacy, comfort, or usage experience (via oral irritation or toothsensitivity for example) in certain doses; and this may vary from doseto dose, and/or over time. Specifically, if for example, a substantialportion of the bleaching agent has macroscopically separated intomultiple visual phases, a dose that is disproportionately rich in thisphase may cause oral irritation or tooth sensitivity when it comes incontact with the oral soft tissue or teeth, while a dose that isdisproportionately poor in this phase may deliver decreased bleachingefficacy. Both these conditions can be undesirable because one can leadto higher discomfort, and the other leads to lower efficacy.

The macroscopic separation of one or more of the components of themulti-phase oral care composition measured according to the methodspecified herein after 2 days at 23° C. or 60° C. can be less than about20%, less than about 10%, less than about 5%, or preferably less thanabout 2%, by weight or volume of the multi-phase oral care composition.

The bleaching efficacy of the present invention, as measured per theclinical protocol disclosed herein, and calculated as −Δb* may be atleast about 0.25, preferably at least about 0.5, more preferred at leastabout 1.0, even more preferred at least about 1.5, even more preferredat least about 2, even more preferred at least about 2.5, even morepreferred at least about 3, even more preferred at least about 3.5, andeven more preferred at least about 4, or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.Generally, a change in yellowness, as measured per the clinical protocolas disclosed herein, and calculated as −Δb* of at least 0.25 isnoticeable.

The present invention can deliver a surprisingly high ratio of bleachingefficacy of the present invention, as measured per the clinical protocoldisclosed herein, and calculated as −Δb*, to the weight percent ofbleaching agent present in the overall multi-phase oral carecomposition. For example, a −Δb* of 1.5 with a composition containing 3%of bleaching agent, would deliver a ratio of bleaching efficacy, asmeasured per the clinical protocol as disclosed herein, and calculatedas −Δb*, to the weight percent of bleaching agent present in the overallmulti-phase oral care composition of 0.5.

The ratio of bleaching efficacy of the present invention, as measuredper the clinical protocol disclosed herein, and calculated as −Δb* tothe weight percent of bleaching agent present in the overall multi-phaseoral care composition may be at least about 2.5, preferably at leastabout 5, more preferred at least about 10, even more preferred at leastabout 15.

The bleaching efficacy of the present invention, as measured per theclinical protocol disclosed herein and calculated as −Δb* may be atleast about 10%, at least about 100%, at least about 1000%, or at leastabout 10,000% more than the bleaching efficacy of a comparative oralcare composition in the form of an aqueous solution or aqueous gel. Thecomparative oral care composition comprises the same bleaching agent atthe same overall concentration dissolved into the aqueous solution oraqueous gel.

The present invention delivers: 1) a surprisingly high ratio ofbleaching efficacy, as measured per the clinical protocol as disclosedherein, and calculated as −Δb*, to the fraction of participants whoreported oral irritation or were observed to have oral irritation thatwas possibly or probably attributed to the composition tested; 2) asurprisingly high ratio of bleaching efficacy of the present invention,as measured per the clinical protocol as disclosed herein, andcalculated as −Δb* to the fraction of participants who reported toothsensitivity that was possibly or probably attributed to the composition;or 3) a surprisingly high ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb*, to the fraction of participants who reportedtooth sensitivity or reported oral irritation or were observed to haveoral irritation that was possibly or probably attributed to thecomposition.

The ratio of bleaching efficacy of the present invention, as measuredper the clinical protocol as disclosed herein, and calculated as −Δb*,to the fraction of participants who report tooth sensitivity that ispossibly or probably attributed to the present invention may be at leastabout 1, at least about 2, at least about 5, at least about 6,preferably at least about 7, more preferred at least about 8, even morepreferred at least about 9, even more preferred at least about 10, evenmore preferred at least about 15, even more preferred at least about 20,even more preferred at least about 25, and even more preferred at leastabout 50, or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

The ratio of bleaching efficacy of the present invention, as measuredper the clinical protocol as disclosed herein, and calculated as −Δb*,to the fraction of participants who report oral irritation or areobserved to have oral irritation that is possibly or probably attributedto the present invention may be at least about 1, at least about 2, atleast about 5, at least about 6, preferably at least about 7, morepreferred at least about 8, even more preferred at least about 9, evenmore preferred at least about 10, even more preferred at least about 15,even more preferred at least about 20, even more preferred at leastabout 25, and even more preferred at least about 50, or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

The ratio of bleaching efficacy of the present invention, as disclosedherein, and calculated as −Δb*, to the fraction of participants whoreport tooth sensitivity or report oral irritation or are observed tohave oral irritation that is possibly or probably attributed to thepresent invention may be at least about 6, preferably at least about 7,more preferred at least about 8, even more preferred at least about 9,even more preferred at least about 10, even more preferred at leastabout 15, even more preferred at least about 20, even more preferred atleast about 25, and even more preferred at least about 50, or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

The residual peroxide intensity of the multi-phase oral carecomposition, as described herein, can be up to about 200, up to about100, or preferably up to about 10.

Delivery Carrier

The present invention may further be related to a delivery system ormethods for delivering the multi-phase oral care compositions and/orjammed oil-in-water emulsion directly to the oral cavity or at least onetooth within the oral cavity of a consumer. The multi-phase compositionscan be used in combination with a re-usable delivery carrier, such as atray, mouth guard, retainer, or combinations thereof. As the deliverycarrier may be re-usable, it is desirable for the multi-phase oral carecomposition to be rinseable or water-dispersible, as described herein.The multi-phase compositions can also be used in combination with adisposable or single-use delivery carrier, such as a disposable strip.

For example, the delivery system may comprise a first layer of a carriermaterial and a second layer comprising a multi-phase oral carecomposition described herein, whereby the bleaching agent is releasablylocated within the present composition. A suitable first layer maycomprise a delivery carrier including a strip of material, a dentaltray, a sponge material, and mixtures thereof. The delivery carrier maybe a strip of material, such as a permanently deformable strip. Suitablestrips of material or permanently deformable strips are for exampledisclosed in U.S. Pat. Nos. 6,136,297; 6,096,328; 5,894,017; 5,891,453;and 5,879,691; and in U.S. Pat. Nos. 5,989,569 and 6,045,811; and inpatent application US 2014/0178443 A1.

The delivery carrier may be attached to the teeth via an attachmentmeans that is part of the delivery carrier, for example the deliverycarrier may be of sufficient size that, once applied the deliverycarrier overlaps with the oral soft tissues rendering more of the teethsurface available for bleaching. The delivery carrier may also beattached to the oral cavity by physical interference or mechanicalinter-locking between the delivery carrier and the oral surfacesincluding the teeth.

The delivery carrier maybe transparent or translucent to electromagneticradiation with wavelengths from about 200 nm to about 1700 nm. Thedelivery carrier can allow from about 10%, 20%, or 30% to about 40%,50%, 60%, 70%, 80%, 90%, or 100% of electromagnetic radiation from about1 nm to about 750 nm, 400 nm to about 500 nm, or from about 250 nm toabout 700 nm to pass through.

The delivery carrier may comprise a dissolvable film, such as thedissolvable film strip disclosed in U.S. Pat. No. 6,709,671, which canbe adhered to the oral cavity thereby releasing an active, thedissolvable film comprising water-soluble polymers, one or morepolyalcohols, and one or more actives. In addition to one or moreactives, a dissolvable film may contain a combination of certainplasticizers or surfactants, colorants, sweetening agents, flavors,flavor enhancers, or other excipients commonly used to modify the tasteof formulations intended for application to the oral cavity. Theresulting dissolvable film is characterized by an instant wettabilitywhich causes the dissolvable film to soften soon after application tothe mucosal tissue, thus preventing the patient from experiencing anyprolonged adverse feeling in the mouth, and a tensile strength suitablefor normal coating, cutting, slitting, and packaging operations.

The dissolvable film may comprise a water-soluble polymer or acombination of water-soluble polymers, one or more plasticizers orsurfactants, one or more polyalcohols, and an active. The polymers usedfor the dissolvable film include polymers which are hydrophilic and/orwater-dispersible. Examples of polymers that can be used includepolymers that are water-soluble cellulose-derivatives, such ashydroxypropylmethyl cellulose, hydroxyethyl cellulose, or hydroxypropylcellulose, either alone, or mixtures thereof. Other optional polymers,without limiting the invention, include polyvinyl pyrrolidone,carboxymethyl cellulose, polyvinyl alcohol, sodium alginate,polyethylene glycol, natural gums like xanthan gum, tragacantha, guargum, acacia gum, arabic gum, water-dispersible polyacrylates likepolyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers.The concentration of the water-soluble polymer in the final film canvery between 20 and 75% (w/w), or between 50 and 75% (w/w).

The strip of material may contain shallow pockets. When the multi-phaseoral care composition is coated on a strip of material, bleach agentsand/or oral care actives, fill shallow pockets to provide reservoirs ofadditional bleach agents and/or oral care actives. Additionally, theshallow pockets help to provide texture to the delivery system. Thestrip of material may have an array of shallow pockets. Generally, theshallow pockets are approximately 0.4 mm across and about 0.1 mm deep.When shallow pockets are included in the strip of material andmulti-phase oral care compositions herein are applied to it in variousthicknesses, such as an overall thickness of the delivery system of lessthan about 1 mm, or preferably less than about 0.5 mm.

The delivery systems as used herein may comprise an adhesion means, suchthat they are capable of adhesion to oral surfaces, especially theteeth. This adhesion means may be provided by the present compositionsherein or the adhesion means may be provided independently of thecompositions herein (for example the adhesion means is a separate phasefrom the compositions herein where the compositions may also have anadhesive means). The strip of material may be held in place on the oralsurface by adhesive attachment provided by the present composition. Theviscosity and general tackiness of the multi-phase oral care compositionto dry surfaces may cause the strip to be adhesively attached to theoral surface without substantial slippage from the frictional forcescreated by the lips, teeth, tongue, and other oral surfaces rubbingagainst the strip of material while talking drinking, etc. However, thisadhesion to the oral surface may be low enough to allow the strip ofmaterial to be easily removed by the wearer by simply peeling off thestrip of material using one's finger. The delivery system may be easilyremovable from the oral surfaces without the use of an instrument, achemical solvent or agent or excess friction.

In addition, the strip of material may be held in place on the oralsurface by adhesive means and attachment provided by the deliverycarrier itself. For example, the strip of material can extend, attach,and adhere to the oral soft tissue. In addition, an adhesive can beapplied to that portion of the strip of material that will attach thedelivery systems to the oral soft tissue. The delivery carrier may alsobe attached to the oral cavity by physical interference or mechanicalinter-locking between the delivery carrier and the oral surfacesincluding the teeth. In addition, the strip of material may be held inplace by an adhesion means that is independent of the composition of thepresent inventions herein, as disclosed in WO 03/015656.

Suitable adhesion means are known to the skilled person. When theadhesive means, if present, is provided by an adhesive, the adhesive maybe any adhesive which may be used to adhere materials to the toothsurface or to a surface of the oral cavity surfaces. Suitable adhesivesinclude, but are not limited to, skin, gum and muco-adhesives, andshould be able to withstand the moisture, chemicals and enzymes of theoral environment for long enough for the oral care actives and/or bleachto take effect, but may be soluble and/or biodegradable thereafter.Suitable adhesives may for example comprise water soluble polymers,hydrophobic and/or non-water-soluble polymers, pressure and moisturesensitive adhesives, e.g. dry adhesives which become tacky upon contactwith the mouth environment, e.g. under the influence of moisture,chemicals or enzymes etc. in the mouth. Suitable adhesives includenatural gums, synthetic resins, natural or synthetic rubbers, those gumsand polymers listed above under “Thickening Agents”, and various othertacky substances of the kind used in known adhesive tapes, those knownfrom U.S. Pat. No. 2,835,628.

In addition, the delivery system may comprise an optional release liner.Such a release liner may be formed from any material which exhibits lessaffinity for the second layer composition than the second layercomposition exhibits for itself and for the first layer strip ofmaterial. The release liner may comprise a rigid sheet of material suchas polyethylene, paper, polyester, or other material, which is thencoated with a nonstick type material. The release liner may be cut tosubstantially the same size and shape as the strip of material or therelease liner may be cut larger than the strip of material to provide areadily accessible means for separating the material from the strip. Therelease liner may be formed from a brittle material that cracks when thestrip is flexed or from multiple pieces of material or a scored piece ofmaterial. Alternatively, the release liner may be in two overlappingpieces such as a typical adhesive bandage design. A description ofmaterials suitable as release agents is found in Kirk-Othmer,Encyclopedia of Chemical Technology, Fourth Edition, Volume 21, pp.207-218.

The delivery carrier may be a permanently deformable strip of materialhaving a yield point and thickness such that the strip of materialsubstantially conforms to a shape of a tooth via permanent deformationunder a pressure less than about 250,000 Pascals as it has been foundthat wearers will press a strip onto each tooth using one fingertiphaving about one square centimeter surface area. They typically applyforce at each tooth for one second or less with a typical applicationpressure ranging from about 100,000 Pascals to about 250,000 Pascals.

The strip of material can have visco-elastic properties which enable itto creep as well as bend in order to conform across several teeth andaround the arch of the wearer's mouth. It is important that thenecessary permanent deformation occurs under minimum normal force beingapplied by the wearer.

The multi-phase oral care composition may also be applied to the toothsurface and may be covered with the deformable strip before or after ithas been shaped. In addition or alternatively, the multi-phase oral carecomposition may be applied to the deformable strip as pre-coating andmay be applied together with the strip to the tooth surface before orafter the deformable strip has been shaped, wherein the strip is appliedsuch that when the delivery system is placed on a surface of the tooth,the multi-phase oral care composition contacts the tooth surfaceproviding an active onto the tooth surface. In addition oralternatively, the deformable strip of material may be applied to theteeth with a force sufficient to shape the delivery carrier such that itat least partially conforms to the shape of the teeth, then the shapedstrip of material may be removed from the tooth surface, the oral carecomposition may be applied to the shaped strip of material, and theshaped strip of material may be re-applied to the tooth surface suchthat it at least partially conforms to a shape of the tooth and contactsthe oral care composition against the tooth surface. If the deformablestrip is applied together with the multi-phase oral care composition tothe tooth surface the multi-phase oral care composition may alsocomprise adhesive agents to hold the delivery system in place for asufficient time to allow the active of the multi-phase oral carecomposition to act upon the surface. The multi-phase oral carecomposition, if used together with a deformable strip, may have anextrusion resistance sufficient to withstand a normal force applied toshape the deformable strip of material so that the substance is notsubstantially extruded from between the deformable strip of material andthe surface during manual shaping of the deformable strip of material.By “substantially extruded from” is meant that at least 50% or more ofthe multi-phase oral care composition is extruded from between thedeformable strip of material and the tooth and adjoining soft tissuesurfaces.

The deformable strip of material may be made of a permanently deformablematerial, such as wax, putty, tin or foil, as a single layer or acombination of layers or materials, such as a laminate. In certainembodiments, the deformable strip may be wax, such as #165 sheet waxformulated and manufactured by Freeman Mfg. & Supply Co. of Cleveland,Ohio. This particular wax readily conforms to the shape of a tooth undera pressure of about 133,000 Pascal which is the pressure generated whenthe wearer applies a normal force of about 3 pounds (1.36 kg) over anarea of about one square centimeter. The deformable strip of materialmay have a nominal film thickness of about 0.8 mm, wherein thedeformable strip may be substantially flat and rectangular in shape withrounded corners. The deformable strip of material may have a lengthsufficient to cover a plurality of adjacent teeth while conforming tothe curvature of the wearer's mouth and gaps between the adjacent teeth.If the deformable strip of material includes the multi-phase oral carecomposition coated thereon, the multi-phase oral care composition mayhave an overall thickness less than about 1.5 mm. Deformable strips asdisclosed herein may also be used as the material for the strip ofmaterial 12 shown in FIGS. 1 to 4. Thus, general features of a strip ofmaterial as described above for example with respect to FIGS. 1 to 4 mayalso apply to the deformable strip of material. In addition, a releaseliner and/or shallow pockets may also be combined with a deformablestrip of material.

The present compositions may be used in combination with a deliverycarrier including a dental tray and/or foam material. Dental trays arewell known in the whitening art. The general process for preparingdental trays 30 is known in the art. Dentists have traditionallyutilized three types of dental appliances for bleaching teeth.

The first type is a rigid appliance which is fitted precisely to thepatient's dental arches. For example, an alginate impression whichregisters all teeth surfaces plus gingival margin is made and a cast ispromptly made of the impression. If reservoirs are desired they areprepared by building a layer of rigid material on the cast on specificteeth surfaces to be treated. A dental tray is then vacuum formed fromthe modified cast using conventional techniques. Once formed, the trayis preferably trimmed barely shy of the gingival margin on both buccaland lingual surfaces. Enough tray material should be left to assure thatall of the tooth will be covered to within about ¼ to about ⅓ mm of thegingival border upon finishing and beveling the tray periphery. One canscallop up and around interdental papilla so that the finished tray doesnot cover them. All tray edges are preferably smoothed so that the lipand tongue will not feel an edge prominence. The resulting tray canprovide a perfect fit of the patient's teeth optionally with reservoirsor spaces located where the rigid material was placed on the cast.Dental trays may comprise of soft transparent vinyl material having apreformed thickness from about 0.1 cm to about 0.15 cm. Soft material ismore comfortable for the patient to wear. Harder material (or thickerplastic) may also be used to construct the tray.

A second type of rigid custom dental appliance is an “oversized” rigidcustom dental appliance. The fabrication of rigid, custom dentalappliances entails fabricating cast models of the patient's dental archimpressions, and heating and vacuum-forming a thermoplastic sheet tocorrespond to the cast models of a patient's dental arches.Thermoplastic films are sold in rigid or semi rigid sheets and areavailable in various sizes and thickness. The dental laboratoryfabrication technique for the oversized rigid dental appliance involvesaugmenting the facial surfaces of the teeth on the cast models withmaterials such as die spacer or light cured acrylics. Next,thermoplastic sheeting is heated and subsequently vacuum formed aroundthe augmented cast models of the dental arch. The net effect of thismethod results in an “oversized” rigid custom dental appliance.

A third type of rigid custom dental appliance, used with less frequency,is a rigid bilaminated custom dental appliance fabricated fromlaminations of materials, ranging from soft porous foams to rigid,non-porous films. The non-porous, rigid thermoplastic shells of thesebilaminated dental appliances encase and support an internal layer ofsoft porous foam.

A fourth type of dental tray replaces rigid custom dental applianceswith disposable U-shaped soft foam trays, which may be individuallypackaged, and which may be saturated with a pre-measured quantity of thecomposition of the present invention. The soft foam material isgenerally an open celled plastic material. Such a device is commerciallyavailable from Cadco Dental Products in Oxnard, Calif. under thetradename VitalWhite™. These soft foam trays may comprise a backingmaterial (e.g. a closed cell plastic backing material) to minimize theelution of the bleaching agent from the device, into the oral cavity tominimize ingestion by the patient and/or irritation of the oral cavitytissues. Alternatively, the soft foam tray is encased by a nonporousflexible polymer or the open cell foam is attached to the frontal innerwall of the dental appliance and/or the open cell foam is attached tothe rear inner wall of the dental appliance. Those of ordinary skill inthe art will readily recognize and appreciate, that the presentcompositions must be thick enough not to simply run out between the opencell structure of the foam and must be thin enough to slowly passthrough the open cell foam over time. In other words, the open cell foammaterial has an internal structural spacing sized relative to theviscosity of the compositions to absorb and allow the composition topass there through.

An example of a closed cell material is a closed-cell polyolefin foamsold by the Voltek division of Sekisui America Corporation of Lawrence,Mass. under the tradename Volora which is from 1/32″ to ⅛″ in thickness.A closed cell material may also comprise of a flexible polymericmaterial. An example of an opened cell material is an open celledpolyethylene foam sold by the Sentinel Foam Products division ofPackaging Industries Group, Inc. of Hyannis, Mass. under the tradenameOpcell which is from 1/16″ to ⅜″ in thickness. Other open cell foamuseful herein include hydrophilic open foam materials such as hydrogelpolymers (e.g Medicell™ foam available from Hydromer, Inc. Branchburg,J. J.). Open cell foam may also be hydrophilic open foam materialimbibed with agents to impart high absorption of fluids, such aspolyurethane or polyvinylpyrrolidone chemically imbibed with variousagents.

In certain aspects, the tray may have pockets built into the surfacecovering or contacting one or more teeth. Such pockets may help hold theoral composition in contact with the teeth. The pockets may be fromabout 0.05 to about 5 mm deep, preferably from about 0.1 to about 3 mmdeep, more preferably from about 0.3 to about 3 mm deep, or mostpreferably from about 0.5 to about 1.5 mm deep. Examples of such traysinclude those specified in the Clinical Protocol section.

In addition, or alternatively, the fit of the tray to the teeth may havea tolerance or gap built into it on one or more teeth. Such as toleranceor gap may help hold the oral composition in contact with the teeth. Thetolerance or gap may be from about 0.01 mm to about 2 mm, preferablyfrom about 0.05 mm to about 1 mm, more preferably from about 0.1 mm toabout 1 mm, or most preferably from about 0.1 mm to about 0.5 mm.

Clinical Protocol

The bleaching efficacies of compositions are measured according to thefollowing clinical protocol. Per treatment group, 17 to 25 participantsare recruited to complete the clinical study when testing compositionswith less than about 1% bleaching agent, and 8 to 25 participants whentesting compositions with at least about 1% bleaching agent. Recruitedparticipants must have four natural maxillary incisors with allmeasurable facial sites. The mean baseline L* of the group ofparticipants must be from 71 to 76, and the mean baseline b* of thegroup of participants must be from 13 to 18. In addition, participantswith malocclusion on maxillary anterior teeth, severe or atypicalintrinsic staining, such as that caused by tetracycline, fluorosis orhypo-calcification, dental crowns or restorations on the facial surfacesof maxillary anterior teeth, self-reported medical history of melanoma,current smoking or tobacco use, light-sensitivity or a pigmentation skindisorder, self-reported tooth sensitivity, or previous tooth whiteningusing a professional treatment, over-the-counter kit, or investigationalproduct, are excluded from the study. Participants are provided withtake-home kits with Crest Cavity Protection toothpaste and Oral-BIndicator soft manual toothbrush (both from Procter & Gamble,Cincinnati, Ohio, USA) to be used twice a day in the customary manner.

The participants use a toothbrush (“Anchor 41 tuft white toothbrush”from Team Technologies, Inc. Morristown, Tenn., USA) to brush theirteeth with water for 30 seconds prior to being treated with thecomposition.

The maxillary anterior teeth of the participants are treated with thecomposition for 60 minutes once daily using a tray with pockets as thedelivery carrier. Specifically, about 0.1 ml of the composition isapplied to each pocket using a syringe (BD 1 ml TB syringe with Slip-TipREF 309659, purchased from VWR, Batavia, Ill.) on the facial surface of8 maxillary anterior teeth of the tray (generally this translates to atotal dose of about 0.7 gram per application). A trained hygienist thencarefully fits the tray onto the maxillary teeth within 1 minute, takingcare not to tilt the composition out of the pockets.

The tray with pockets is made using the following procedure:

-   -   An impression is taken of the maxillary arch. The impression is        poured with dental stone. About 1 to 1.5 mm thick layer of        block-out material (Premier Perfecta Block-out) is applied to        the facial surfaces of the anterior teeth of the stone model        leaving about 0.5 mm from the mesial edge. The block-out        material is cured for at least 5 seconds after applying to every        2 teeth. This is repeated for all anterior teeth.    -   Pro-form tray material (Keystone Vacuum Forming Material        Pro-form, Soft EVA 1 mm, Clear) is heated with a vacuum former.        Once the material sags about 1 inch, it is pulled down on top of        the stone model and held under vacuum for at least 15 seconds,        cooled, and the stone model is carefully removed. The tray is        then trimmed to desired fit.        Within each 60-minute treatment, the composition is re-applied        to the tray every 20 minutes for a total of 3×20-minute        applications. The three 20-minute applications are applied        back-to-back for a total of 60 minutes per treatment, once        daily.        Electromagnetic radiation is applied as follows:    -   1) Within each 20-minute application, a trained hygienist        applies electromagnetic radiation toward the facial surfaces of        the maxillary anterior teeth during the last 10 minutes.    -   2) The electromagnetic radiation is directed toward the        maxillary anterior teeth through the tray and through the        composition,    -   3) The tray needs to allow at least about 90% of the        electromagnetic radiation from 400 nm to 500 nm to pass through,        and    -   4) The electromagnetic radiation is delivered via four        fiber-optic cables (model number M71L01 from Thorlabs, Newton,        N.J., USA) connected to four high power LEDs with a peak        intensity wavelength of 455 nm (model number M455F1 from        Thorlabs, Newton, N.J., USA) as shown in FIG. 6. The four LEDs        are run at 1000 mA each using an LED Driver and Hub (model        numbers DC4104 and DC4100-HUB from Thorlabs, Newton, N.J., USA).        The exit ends of the four fiber-optic cables are mounted behind        a transparent mouthpiece to help position the electromagnetic        radiation reproducibly against the outer surface of the strip.        The exit ends of the four fiber-optic cables are about 7 mm away        from the exit surface of the mouthpiece with the electromagnetic        radiation passing through the transparent mouthpiece. The        bite-shelf of the mouthpiece is offset such that the transparent        window through which the electromagnetic radiation passes toward        the maxillary anterior teeth is 7.4 mm high. Also, the        transparent window through which the electromagnetic radiation        passes toward the maxillary anterior teeth is 40 mm long        measured linearly from end to end (not including the curvature).        The exit ends of the fiber-optic cables are positioned and        angled such that the cones of electromagnetic radiation exiting        from the fiber-optic cables are centered within the transparent        window through which the electromagnetic radiation passes toward        the maxillary anterior teeth as shown in FIG. 6. Also, the exit        ends of the four fiber-optic cables are spaced such that the        cones of electromagnetic radiation are spaced across the length        of the transparent window through which the electromagnetic        radiation passes toward the maxillary anterior teeth as shown in        FIG. 6. The intensity of the electromagnetic radiation from 400        nm to 500 nm measured at the central axis of each cone of        electromagnetic radiation exiting at the exit surface of the        transparent window through which the electromagnetic radiation        passes toward the maxillary anterior teeth needs to be from        about 175 mW/cm² to about 225 mW/cm² as measured by the method        disclosed herein.

Once 60 minutes of the treatment with the composition is completed, thetray is removed. This treatment is applied once daily for a minimum of 7days for compositions with less than about 1% bleaching agent, and aminimum of 3 days for compositions with at least about 1% bleachingagent.

The change in tooth color due to the treatment with the composition ismeasured using the procedure described below the day after the 7^(th)treatment for compositions with less than about 1% bleaching agent andthe day after the 3^(rd) treatment for compositions with at least about1% bleaching agent.

Tooth color is measured using a digital camera having a lens equippedwith a polarizer filter (Camera model no. CANON EOS 70D from Canon Inc.,Melville, N.Y. with NIKON 55 mm micro-NIKKOR lens with adapter). Thelight system is provided by Dedo lights (model number DLH2) equippedwith 150 watt, 24V bulbs model number (Xenophot model number HL X64640),positioned about 30 cm apart (measured from the center of the externalcircular surface of one of the glass lens through which the light exitsto the other) and aimed at a 45 degree angle, such that the light pathsintersect at the vertical plane of the chin rest about 36 cm in front ofthe focal plane of the camera. Each light has a polarizing filter (Lee201 filter), and a cutoff filter (Rosco 7 mil Thermashield filter fromRosco, Stamford, Conn., USA).

At the intersection of the light paths, a fixed chin rest is mounted forreproducible repositioning in the light field. The camera is placedbetween the two lights such that its focal plane is about 36 cm from thevertical plane of the chin rest. Prior to beginning the measurement oftooth color, color standards are imaged to establish calibrationset-points. A Munsell N8 grey standard is imaged first. The whitebalance of the camera is adjusted, such that the RGB values of grey are200. Color standards are imaged to get standard RGB values of the colorchips. The color standards and grey standard are listed below (fromMunsell Color, Division of X-rite, Grand Rapids, Mich., USA). Each colorstandard is labeled with the Munsell nomenclature. To create a grid ofcolor standards they can be arranged in the following manner. Thisenables multiple color standards to be contained in a single imagecaptured of the grid of color standards.

Color standard grid 1 7.5R 6 8 2.5R 6 10 10YR 6.5 3 POLARIZATION CHECK5R 7 8 N 3.5 0 7.5RP 6 6 10R 5 8 5YR 7 3 2.5Y 8.5 2 2.2YR 6.47 4.1 7.5YR7 4 5YR 8 2 N 8 0 10R 7 4 N 8 0 5YR 7.5 2.5 2.5Y 8 4 5YR 7 3.5 5YR 7 2.55YR 5 2 5YR 7.5 2 N 6.5 0 N 9.5 0

Color standard grid 2 5YR 7.5 3.5 2.5Y 6 4 10YR 7.5 3.5 2.5R 7 8 7.5R 78 10YR 7.5 2 10YR 7.5 2.5 N 5 0 2.5R 6 8 10YR 7 2 5R 7 4 10YR 7 2.5 N6.5 0 7.5RP 6 8 7.5R 8 4 5Y 8 1 7.5YR 8 2 2.2YR 6.47 4.1 N 5 0 2.5Y 8 410YR 7 3 N 9.5 0 10RP 7 4 2.5Y 7 2

Color standard grid 3 5R 6 10 N 8.5 0 10YR 6.5 3.5 10RP 6 10 N 8 0 7.5YR7 3 2.5Y 3.5 0 10YR 7 3.5 5Y 8.5 1 5YR 8 2.5 5YR 7.5 3 5R 5 6 10YR 7.5 35YR 6.5 3.5 2.5YR 5 4 2.5Y 8 2 10YR 8 2 2.5Y 7 2 2.5R 6 6 5R 7 6 10YR 82.5 10R 5 6 N 6.5 0 7.5YR 8 3

For baseline tooth color, participants use a toothbrush (“Anchor 41 tuftwhite toothbrush” from Team Technologies, Inc. Morristown, Tenn., USA)to brush their teeth with water to remove debris from their teeth. Eachparticipant then uses cheek retractors (from Washington ScientificCamera Company, Sumner, Wash., USA; treated with at frosted matte finishat A&B Deburring Company, Cincinnati, Ohio, USA) to pull the cheeks backand allow the facial surfaces of their teeth to be illuminated. Eachparticipant is instructed to bite their teeth together such that theincisal edges of the maxillary incisors contact the incisal edges of themandibular incisors. The participants are then positioned on the chinrest at the intersection of the light paths in the center of the cameraview and the tooth images are captured. After all participants areimaged, the images are processed using image analysis software (Optimasmanufactured by Media Cybernetics, Inc. of Silver Spring, Md.). Thecentral four incisors are isolated and the average RGB values of theteeth are extracted.

After the participants have used a whitening product, but prior tocapturing participant's tooth images, the system is set to the baselineconfiguration and calibrated as previously discussed. After calibration,each participant is imaged a second time using the same procedure asbefore making sure the participant is in the same physical position asthe pre-treatment image including orientation of the teeth. The imagesare processed using the image analysis software to obtain the averageRGB values of the central four maxillary incisors. The RGB values of allof the images are then mapped into CIE L*′a*b* color space using the RGBvalues and the L*a*b* values of the color chips on the color standard.The L*a*b* values of the color chips on the color standard are measuredusing a Photo Research SpectraScan PR650 from Photo Research Inc., LAusing the same lighting conditions described for capturing digitalimages of the facial dentition. The PR650 is positioned the samedistance from the color standards as the camera. Each chip isindividually measured for L*a*b* after calibration according to themanufacturer's instructions. The RGB values are then transformed intoL*a*b* values using regression equations such as:L*=25.16+12.02*(R/100)+11.75*(G/100)−2.75*(B/100)+1.95*(G/100)³a*=−2.65+59.22*(R/100)−50.52*(G/100)+0.20*(B/100)−29.87*(R/100)²+20.73*(G/100)²+8.14*(R/100)³−9.17(G/100)³+3.64*[(B/100)²]*[R/100]b*=−0.70+37.04*(R/100)+12.65*(G/100)−53.81*(B/100)−18.14*(R/100)²+23.16*(G/100)*(B/100)+4.70*(R/100)³−6.45*(B/100)³The R² for L*, a*, and b* should be >0.95. Each study should have itsown equations.

These equations are generally valid transformations in the area of toothcolor (60<L*<95, 0<a*<14, 6<b*<25). The data from each participant's setof images is then used to calculate product whitening performance interms of changes in L*, a* and b*—a standard method used for assessingwhitening benefits. When evaluating compositions with less than about 1%bleaching agent: Changes in L* is defined asΔL*=L*_(day after 7 treatments)−L*_(baseline) where a positive changeindicates improvement in brightness; Changes in a* (red-green balance)is defined as Δa*=a*_(day after 7 treatments)−a*_(baseline) where anegative change indicates teeth which are less red; Changes in b*(yellow-blue balance) is defined asΔb*=b*_(day after 7 treatments)−b*_(baseline) where a negative changeindicates teeth are becoming less yellow. When evaluating compositionswith at least about 1% bleaching agent: Changes in L* is defined asΔL*=L*_(day after 3 treatments)−L*_(baseline) where a positive changeindicates improvement in brightness; Changes in a* (red-green balance)is defined as Δa*=a*_(day after 3 treatments)−a*_(baseline) where anegative change indicates teeth which are less red; Changes in b*(yellow-blue balance) is defined asΔb*=b*_(day after 3 treatments)−b*baseline where a negative changeindicates teeth are becoming less yellow. −Δb* is used as the primarymeasure of bleaching efficacy. The overall color change is calculated bythe equation ΔE=(ΔL*²+Δa*²+Δb*²)^(1/2).

After using the whitening products, color changes in CIE Lab color spacecan be calculated for each participant based on the equations given.

To validate the above clinical protocol, the bleaching efficacy(calculated as −Δb*) of Example I-B made according to the procedurespecified herein (delivered on a tray with pockets and used withelectromagnetic radiation as disclosed herein) needs to be measured theday after the 3^(rd) treatment and demonstrated to be >3

Preparation of the Present Multi-Phase Oral Care Compositions

Preparation of emulsions is well known in the art and any suitablemanufacturing process can be used to make the multi-phase oral carecompositions which may be in the form of an emulsion; see for example,Remington: the Science and Practice of Pharmacy, 19^(th) ed., Vol. II,Chapters 20, 80, 86, etc. Generally, the components are separated intothose that are oil-soluble and those that are water-soluble. These aredissolved in their respective solvents by heating if necessary. The twophases are then mixed and the product is stirred and cooled. Aftercombining the phases, the present multi-phase oral care compositions,which may be in the form of emulsions may be agitated or sheared byvarious methods, including shaking, intermittent shaking, high shearmixing, or by using high speed mixers, blenders, colloid mills,homogenizers, or ultrasonic techniques. Depending on the specificingredients, it may be recognized by one of skill in the art thatcertain modifications may need to be made to the manufacturing processto accommodate the specific properties of the ingredients. The type ofmulti-phase oral care composition prepared may be observed using amicroscope. Further description of test methods are disclosed inRemington: The Science and Practice of Pharmacy, 19^(th) ed., volume 1,1995, pp. 282-283.

In certain aspects, multi-phase oral care compositions, which may be inthe form of a jammed oil-in-water emulsion, as disclosed herein may bemade as follows:

-   -   1) The water-soluble ingredients are dissolved in the aqueous        phase, and the oil-soluble components in the hydrophobic phase.    -   2) The hydrophobic phase is added to the aqueous phase in        portions in a SpeedMixer container with thorough mixing (with a        rubber spatula for about 1 to 2 minutes for example, depending        on the size of the batch) between portions. Ideally, 1) the size        of the initial portion is less than 20% of the amount aqueous        phase, 2) the size of subsequent portions may be increased        gradually toward the amount of aqueous phase, and 3) the size of        each portion is less than the amount of aqueous phase. As the        jamming concentration is approached, an oil-in-water emulsion        forms during this step, and the composition develops a        lotion-like semisolid consistency—this is evidence that the        droplets of the hydrophobic phase are jammed against each other        and deform each other (note, they are still separated by a        region of aqueous phase). This jamming is evidenced by the        development of a lotion-like consistency of the composition.    -   3) Once all the hydrophobic phase has been incorporated, the        contents of the Speedmixer container are mixed 3 times at 800        RPM for 2 minutes each time in a Speedmixer.

Note, in certain aspects, 1) it may be possible to add the hydrophobicphase to the aqueous phase at a suitably slow but continuous or pulsedrate with concurrent mixing in step-2 above, and 2) the mixing in step-3above may be accomplished with other types of mixers over variouslengths of time, such as a recirculation loop through static mixers,rotor-stator mixers, or other mixing devices, such as those described inthe Handbook of Industrial Mixing.

The mixing procedure of the SpeedMixer™ series is based on the doublerotation of the mixing cup using a dual asymmetric centrifugal mixing.This combination of centrifugal forces acting on different levelsenables very rapid mixing of the entire cup. Optionally the compositionmay be heated, if necessary, to facilitate mixing. When the active isincluded in solid particulate form, the addition of an optionalviscosity modifier, may be appropriate to keep the particulate dispersedand suspended within the composition. Flavorants or sweeteners may alsobe added to one of the phases of the composition, as desired. Thereafterthe composition may be added to the delivery carrier, as desired.

Methods of Using the Compositions and/or Delivery Systems

The present invention can be applied to the teeth of a consumer in thedental office by a dental professional, or the present invention can beapplied at home by the consumer. Generally, the recommended treatmentperiod is a sufficient period of time to achieve whitening.

In practicing the present invention, the patient applies the multi-phaseoral care composition or jammed oil-in-water emulsion, as describedherein, that contains the bleaching agent to obtain the desired effect,such as, whitening, to one or more teeth. The composition can be appliedwith a paint-on device, a syringe or unit dose syringe, squeezable tube,a brush, a pen or brush tip applicator, a doe's foot applicator, swab,lip gloss applicator, strip that is removed after application, tray thatis removed after application, or the like, or even with the fingers. Thecomposition can also be combined with a delivery carrier, such as astrip of material, a dental tray, or a sponge material, and thereafterapplied to the teeth. In certain aspects, the compositions or deliverysystems herein are almost unnoticeable when applied to the teeth. Aftera desired period of time has elapsed, any residual composition may beeasily removed by wiping, brushing or rinsing the oral surface.

In general, it is not necessary to prepare the teeth before applying thepresent composition. For example, the patient may choose to brush theteeth or rinse the mouth before applying the compositions of the presentinvention, but the surfaces of the oral cavity are neither required tobe clean, to be dried, nor to be excessively wet with saliva or waterbefore the application. However, it is believed that adhesion to thetooth enamel surfaces can be improved if the teeth are dry prior toapplication.

Dental tray appliances may be used as follows. The patient or dentalprofessional dispenses the present composition into a soft or rigiddental appliance and then the participant places the appliance over theparticipant's dental arch (or fits the device around his or her teeth tokeep the tray in position). Generally, the recommended treatment periodis a sufficient period of time to achieve whitening as disclosed above.At the end of the treatment period, the dental appliance is removed,cleaned with water to remove any remaining composition, and then storeduntil the next application.

The described compositions and delivery systems, described herein, maybe combined in a kit which comprises: 1. present composition and 2.instructions for use; or which comprises: 1. present composition, 2.instructions for use, and 3. a delivery carrier. In addition, if thetooth shall be radiated by electromagnetic radiation, the kit mayfurther comprise an electromagnetic radiation source of the appropriatewavelength and instruction for use, so that the kit can be used byconsumers in a convenient manner.

Optional Electromagnetic Radiation Treatment

The multi-phase oral care composition as disclosed herein may be used towhiten teeth and/or removing stain from tooth surfaces. In addition, thebleaching efficacy may be further increased by directing electromagneticradiation of a suitable wavelength toward at least one tooth. A suitablewavelength may be any wavelength, which corresponds to a maximumabsorption band of the tooth and/or the tooth stain to be bleached. Forexample, the multi-phase oral care composition may be radiated with anelectromagnetic radiation with one or more wavelengths in the range offrom about 200 nm to about 1200 nm. The electromagnetic radiation may bedirected toward at least one tooth. In addition, more than one tooth maybe irradiated. For example, the electromagnetic radiation may have apeak intensity at one or more wavelengths in the range of from about 1nm to about 750 nm, from about 200 nm to about 700 nm, from about 300 nmto about 700 nm, from about 400 nm to about 600 nm, from about 400 nm toabout 500 nm, or up to about 750 nm. Additionally, the electromagneticradiation may have a peak intensity at one or more wavelengths in therange of from about 400, 405, 410, 415, 420, 425, 430, 435, 440, or 445,446 nm to about 450, 455, 460, 465, 470, 475, 480, 481, 485, 490, 495,or 500 nm or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein. The electromagnetic radiationcan have a peak intensity at a wavelength in the range of from about 425nm to about 475 nm, from about 445 nm to about 465 nm, or wherein thepeak intensity wavelength of the electromagnetic radiation is similar tothe wavelength at which the stain absorbs the most electromagneticradiation. Electromagnetic radiation may be directed toward at least onetooth for partial or whole wearing time of the composition; or after thecomposition has been removed from the tooth. Electromagnetic radiationmay be applied at least for a sufficient period of time for whitening,e.g. for at least about 1 minute, for at least about 5 minutes, or forat least about 10 min. The electromagnetic radiation may be appliedusing the procedure disclosed in US 2013/0295525. Preferably themulti-phase oral care composition as disclosed herein is applied to atleast one tooth and maintained on the at least one tooth for a firstperiod of time; after the first period of time electromagnetic radiationis directed toward the at least one tooth for a second period of time,wherein the first period of time has a duration greater than 50%,preferably 80% of a total duration of the first and second periods oftime; and finally, the multi-phase oral care composition is removed fromthe at least one tooth. Suitable sources of electromagnetic radiationinclude the sources described herein.

The multi-phase oral care compositions as disclosed herein may betransparent or translucent to electromagnetic radiation with wavelengthsfrom about 400 nm to about 500 nm. In certain aspects, the multi-phaseoral care compositions as disclosed herein when applied in a thicknessof from about 0.0001, 0.001, or 0.01 cm to about 0.01, 0.1, or 0.5 cmthick allow from about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%,80%, 90%, or 100% of electromagnetic radiation at one or morewavelengths in the range of from about 1 nm to about 750 nm, from about200 nm to about 700 nm, from about 300 nm to about 700 nm, from about400 nm to about 600 nm, from about 400 nm to about 500 nm, or up toabout 750 nm to pass through, as measured by a spectrophotometer. When amulti-phase oral care composition is applied in a thickness of about 0.1cm, from about 80% to about 100% of electromagnetic radiation from about400 nm to about 500 nm can pass through, as measured by aspectrophotometer. The multi-phase oral care compositions, as disclosedherein, may when applied in an amount from about 0.0001, 0.001, or 0.01grams to about 0.01, 0.1, 1, or 5 grams, on a delivery carrier or traywith a surface area from about 5 cm² to about 20 cm², allow from about10%, 20%, or 30% to about 40%, 50%, 60%, 70%, 80%, 90%, or 100% ofelectromagnetic radiation from about 400 nm to about 500 nm to passthrough.

The electromagnetic radiation impinging on the surface of the tooth orouter surface of the carrier, which may be a strip or tray, at one ormore wavelengths in the range of from about 1 nm to about 750 nm, fromabout 200 nm to about 700 nm, from about 300 nm to about 700 nm, fromabout 400 nm to about 600 nm, from about 400 nm to about 500 nm, or upto about 750 nm. may range in intensity from about 5, 10, 25, 50, 75, or100 mW/cm² to about 10000, 5000, 2000, 1000, 500, 250, 225, 205, 200,175, 150, 125, 100, 75, 50, 25, 10, or 5 mW/cm² or any other numericalrange, which is narrower and which falls within such broader numericalrange, as if such narrower numerical ranges were all expressly writtenherein.

The intensity of the electromagnetic radiation can be measured using aspectrometer (USB 2000+ from Ocean Optics) connected to a UV-VIS 200micron fiber-optic cable with a cosine corrector at the tip (OP200-2-UV-VIS from Ocean Optics). The spectrometer is connected to acomputer running the spectrometer software (Oceanview 1.3.4 from OceanOptics). The tip of the fiber-optic cable is held pointing toward thelight source at the location where the light intensity is to bemeasured. The photons collected at the detector surface are guided viathe fiber-optic cable to the charge-coupled device in the spectrometer(CCD). The CCD counts photons arriving to the CCD during apre-determined time period at each wavelength from 200 nm to 1100 nm,and uses a software algorithm to convert these photon counts to spectralirradiance (mW/cm²/nm). The spectral irradiance is integrated from 200nm to 1100 nm by the software to yield the Absolute Irradiance (mW/cm²),which is the intensity of electromagnetic radiation from 200 nm to 1100nm. The spectral irradiance is integrated from 400 nm to 500 nm by thesoftware to yield the Absolute Irradiance (mW/cm²), which is theintensity of electromagnetic radiation from 400 nm to 500 nm.

For consumer convenience, the multi-phase oral care composition asdisclosed herein may be provided as a Kit comprising the bleachingcomposition as disclosed herein, a delivery carrier for easierapplication, an electromagnetic radiation source emittingelectromagnetic radiation in a suitable wavelength, and instructions foruse.

The electromagnetic radiation source emitting electromagnetic radiationin a suitable wavelength can be a device capable of producingelectromagnetic radiation, such as the devices described in U.S. Pat.No. 10,099,064, or curing lights used in dental offices, or devicessimilar to that described in the clinical protocol section specifiedherein.

The compositions of this invention are useful for both human and otheranimals (e.g. pets, zoo, or domestic animals) applications.

Methods

Method to Measure the Two-Dimensional Density of Droplets of AqueousPhase or the Two-Dimensional Density of Regions of Hydrophobic Phase ofa Multi-Phase Oral Care Composition

-   -   1. Use a small spatula and place a small sample of the        composition on a glass microscope slide (VWR Micro Slides, Super        Frost Plus, 25×75×1 mm, manufactured by VWR International,        Radnor, Pa.; purchased from VWR, Batavia, Ill., catalog number        48311-703). The amount of sample should be such that after it        has been pressed down per step 2, at least about 100 square        millimeters of the slide are completely covered with the        composition and can be measured. Take care to place the sample        as a single blob on the adhesive grid sticker—this helps        minimize air-entrapment when the coverslip is placed over it.    -   2. Place a coverslip (VWR Microscope Cover Glasses, 22×22 mm,        purchased from VWR, Batavia, Ill., catalog number 16004-094)        over the sample-composition and press down (if needed) until the        sample-composition is about 120 microns thick. Spacers (Electron        Microscopy Sciences, Hatfield Pa., Cat. 70327-20S or 70327-13S)        may be used to control the thickness.    -   3. Place the microscope slide on a microscope and focus on the        sample using light transmitted through the sample. Use a        microscope and a magnification level that enable the measurement        of the cross-sectional area of droplets of aqueous phase or        regions of hydrophobic phase larger than the specified value.    -   4. Count the number of droplets of aqueous phase or regions of        hydrophobic phase whose cross-sectional area at the        two-dimensional focal plane is larger than the specified value.        Take care not to count residual air-bubbles (unlike droplets of        aqueous phase or regions of hydrophobic phase, air bubbles may        be identified by thick dark walls in the field of view).    -   5. The “two-dimensional density of droplets of aqueous phase” or        “two-dimensional density of regions of hydrophobic phase” with a        cross-sectional area larger than a specified value (expressed as        number of droplets of aqueous phase per square centimeter or        number of regions of hydrophobic phase per square centimeter)        for this slide is calculated as: The number of droplets of        aqueous phase or the number of regions of hydrophobic phase        whose cross-sectional area at the two-dimensional focal plane is        larger than the specified value measured in this slide DIVIDED        by the total area of the slide covered by the composition        expressed in square centimeters.    -   6. Repeat steps 1 to 5 for a total of at least twelve slides.        Average the calculation from step 5 across all the slides        measured. This is the final “two-dimensional density of droplets        of aqueous phase” or “two-dimensional density of regions of        hydrophobic phase” with a cross-sectional area larger than a        specified value (expressed as number of droplets of aqueous        phase per square centimeter or number of regions of hydrophobic        phase per square centimeter).        Method to Measure the Dv 50, D[4,3], and D[3,2] of Regions of        Hydrophobic Phase of a Multi-Phase Oral Care Composition    -   1. Weigh 0.20 g (+/−0.02 g) of the sample to be tested into a 20        ml HDPE scintillation vial (VWR 66021-690).    -   2. Add water (for example WFI Quality OmniPur Sterile Filtered        CAS #7732-18-5) 19.80 g (+/−0.02 g) to the vial and secure cap.    -   3. Roll the vial on a countertop gently until the sample to be        tested is dispersed throughout the water. Avoid shaking or        mixing vigorously.    -   4. Set up the Mastersizer 3000 (Malvern Panalytical Inc.,        Westborough, Mass.) and the Hydro unit (Model #MAZ3210), and        ensure the hoses are securely attached.    -   5. Add water (for example MilliporeSigma Ultrapure Lab water        system) to the lowest edge of silver rim and initialize the        system (this measures the background).    -   6. When the system is ready, roll the vial gently about 4 or 5        times to mix the contents, and then slowly pipet contents of the        vial (generally from about 0.1 gram to about 5 grams) using a        1.7 ml pipet (VWR #414004-031) into the Hydro unit until        Obscuration is in range to be measured (1-10%). If the        obscuration % is >10%, remove some of the sample solution from        the vessel and add water (for example MilliporeSigma Ultrapure        Lab water system) until Obscuration is less than 10%.    -   7. Start testing. Testing is done for 10 measurements and the        sample is flushed upon completion. Stirrer speed is set at 500        rpm.    -   8. Add water when indicated for rinsing the system between        samples (water is added generally about 5 to 6 times)    -   9. Repeat testing 2 more times with rinses in between.    -   10. Record the average Dv 50, D[4,3], and D[3,2] for each set of        data (10 measurements×3 replications).

Additional information on the use of the Mastersizer 3000 can be foundin the user manual (MAN0474 MRK1953-0 on the websitemalvernpanalytical.com).

To validate the above method, the D[4,3] of Example I-B made accordingto the procedure specified herein must be measured and demonstrated tobe from 15 microns to 30 microns.

Method to Measure the Water-Dispersibility of a Multi-Phase Oral CareComposition

-   -   1. Allow the multi-phase oral care composition and sterile        filtered water (Calbiochem catalog number 4.86505.1000 from EMD        Millipore Corporation, Billerica, Mass.) to equilibrate at the        desired temperature for at least 12 hours.    -   2. Record the tare weight of the bottom portion of a petri dish        (VWR, Polystyrene, 100 mm×15 mm, catalog number 25384-342,        purchased from VWR, Batavia, Ill.).    -   3. Weigh 0.30 to 0.35 gram of the multi-phase oral care        composition into the center of the petri dish in one single        blob. Record the initial weight of the sample.    -   4. Add 30 ml of sterile filtered water to the petri dish without        disturbing the sample—with a syringe (30 ml BD Syringe with Luer        Lok tip, item number 302832), taking care to go around the edges        of the petri dish and directing the stream away from the sample.    -   5. After 10 minutes, decant the contents of the petri dish, dry        it in an oven set at 60 C for at least 60 minutes, allow it to        cool, and record the weight of petri dish+residual sample.    -   6. Calculate:        Weight of residual sample=(Weight of petri dish+residual sample        from step-5) MINUS (Tare weight of petri dish from step-2)    -   7. Calculate:        Water-dispersibility=100 MINUS [100×(Weight of residual sample        from step-6)/(Initial weight of sample from step-3)]    -   8. Repeat steps-1-7 for a total of at least 3 measurements.        Calculate the average. This is the water-dispersibility of the        multi-phase oral care composition.        To validate the above method, the water-dispersibility of 1)        Example I-B made according to the procedure specified herein        must be measured and demonstrated to be from 60 to 100%, and 2)        Comparative Example VI and Comparative Example VII made        according to the procedure specified herein must be measured and        demonstrated to be from 0 to 10%.        Method to Measure the Mean and Standard Deviation of the        Peroxide Concentration of a Multi-Phase Oral Care Composition        Smeared onto Peroxide Test Strips

-   1. Weigh 0.60 to 0.80 gram of the composition onto the end of a    clean hard rubber spatula (4″ long blade, from VWR, Batavia, Ill.    60510, USA., catalog number 57930-025).

-   2. Take a fresh peroxide test strip (EMD Millipore Corporation,    Billerica, Mass., supplier number 1.16974.0001; purchased from VWR,    Batavia, Ill., catalog number EM1.16974.0001) out of the container,    and start a timer.

-   3. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein. Place the peroxide test strip on a fresh    paper towel.

-   4. Hold the spatula and peroxide test strip. Smear the composition    (pre-weighed in step-1) with firm pressure from left to right onto    both reaction-zones on the test strip. Repeat the smearing motion a    total of three strokes from left to right with the same sample of    composition that has already been pre-weighed onto the spatula.

-   5. Move the peroxide test strip to a clean area of the paper towel.    Place a filter paper (Whatman Grade 1 Qualitative Filter Paper    Standard Grade, circle, 90 mm, supplier number 1001-090; from VWR,    Batavia, Ill. 60510, USA., catalog number 28450-081) on top of the    test strip. Apply finger pressure on top of the filter paper. Pull    the peroxide test strip out from under the filter paper (while    maintaining finger pressure on the filter paper) in a single stroke    such that excess gel is wiped off onto the filter paper and paper    towel. Make sure the reaction-zones do not get dislodged from the    peroxide test strip.

-   6. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein.

-   7. Steps 2 to 6 should be completed within 90 seconds on the timer.

-   8. Repeat steps 1 to 7 for a total of at least eighteen peroxide    test strips.

-   9. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the Red intensities of    the strip of Munsell N8 Matte Color sheet attached to the holder    that serves as a built-in Munsell N8 reference within each image.    The mean R value intensity of the built-in Munsell N8 reference    within each image should be from 204 to 212 and the standard    deviation should be no more than 3.

-   10. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the Red intensities of    each reaction-zone on all peroxide test strips at BASELINE (before    smearing with the composition).

-   11. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the Red intensities of    each reaction-zone on all peroxide test strips AFTER smearing with    the composition.

-   12. The mean peroxide concentration of the composition smeared on    peroxide test strips is calculated as follows: First, calculate the    mean baseline R value intensity of each reaction-zone from step-10    MINUS the mean R value intensity of the same reaction-zone after    smearing with the composition from step-11. Repeat this calculation    for all reaction-zones, and average the results across all    reaction-zones on all peroxide test strips. This is the mean    peroxide concentration of the composition smeared on peroxide test    strips.

-   13. The standard deviation of the peroxide concentration of the    composition smeared on peroxide test strips is calculated as:    Average the standard deviation of the Red intensities across all    reaction-zones on all peroxide test strips AFTER they have been    smeared with the composition from step-11. This is the standard    deviation of the peroxide concentration of the composition smeared    on peroxide test strips.

To validate the equipment, system configuration, and method specifiedherein, the mean and standard deviation of the Red intensities of aMunsell N8 Matte Color sheet (from Munsell Color, Division of X-rite,Grand Rapids, Mich., USA) needs to be measured and demonstrated to befrom 204 to 212 for the mean and no more than 3 for the standarddeviation.

Equipment to Take Digital Images of Peroxide Test Strips

1—Digital camera capable of capturing images at 18 million pixels(5184×3456) resolution jpg image and capable of a shutter speed of11250^(th) of a second (such as Canon 60D camera from Canon

USA Inc., Lake Success, N.Y. 11042)

1—Memory card

1—Lens adapter if needed (such as Canon body to Nikon lens adapter)

1-105 mm lens (such as 105 mm Micro Nikkor lens from Nikon USA Inc.Melville, N.Y. 11747)

1-52 mm Flash adapter ring

1—Macro ring lite with polarization filter attached (such as CanonMR-14EX Macro ring lite with polarization filter attached from Canon USAInc., Lake Success, N.Y. 11042)

1-52 mm Rotating Circular Polarizer on the lens

1—Tripod

1—Sheet Munsell N8 Matte Color sheet (from Munsell Color, Division ofX-rite, Grand Rapids, Mich., USA)

1—Holder for the peroxide test strips made using DGK Plastic Gray cardXL (from DGK Color Tools on Amazon.com) as the background, and a stripof Munsell N8 Matte Color sheet attached to serve as a built-in MunsellN8 reference within each image.

1—mm scale mounted to a blank specimen strip

System Configuration to Take Digital Images of Peroxide Test Strips

-   1. The tripod is configured with the tripod mount attached to the    underside of the tripod to accommodate macro photography, with the    camera pointing down toward the table. The subject plane is 317 mm    from the sensor plane.-   2. The Nikon 105 mm lens is attached to the Canon 60D camera body    using the Canon to Nikon adapter mount.-   3. The rotating polarizer is attached to the 105 mm Micro Nikkor    lens.-   4. The 52 mm flash adapter ring is attached to the front of the 105    mm lens.-   5. The Canon MR-14EX Macro ring lite with polarization filter is    attached to the front of the lens to the flash adapter ring.-   6. The rotating circular polarizer on the lens is rotated until the    maximum gloss/glare is removed and complete cross polarization is    achieved.-   7. The flash is set to ‘manual’ mode with the power setting set to ⅛    power.-   8. The Canon 60D camera is set to ‘manual’ mode with the ISO set to    100.-   9. The Shutter is set to 1/250^(th) of a Second.-   10. The aperture is set at f=8 on the 105 mm Micro Nikkor lens.-   11. Manual Focus is used on the 105 mm Micro Nikkor lens with the    focus to 317 mm distance from the sensor plane to the subject plane.-   12. A mounted sheet of calibrated Munsell N8 material is used to    achieve White Balance for the images.-   13. The camera is set to capture images at the 18 million pixels    (5184×3456) resolution jpg image.-   14. The total exposure setting for the camera and flash needs to be    configured such that a captured image of the Munsell N8 Matte Color    sheet has a mean R value intensity of 204 to 212 and a standard    deviation of no more than 3 measured using the procedure specified    herein.    Procedure in Adobe Photoshop CS4 to Measure the Mean and Standard    Deviation of the Red Intensities-   1. Open Adobe Photoshop CS4.-   2. On the top edge of the screen select “Window”, followed by    “Histogram”. This displays the histogram of the image. In the    Histogram window, select “Expanded view” and “Show statistics”. This    displays the histogram with statistics. Make sure the “Channel” is    set to “Red”. In Adobe Photoshop CS4, a histogram panel displays the    tonal range of an image. It shows how the pixels are distributed by    graphing the number of pixels at each of the 256 intensity levels    from 0-255 in the region of interest selected. Pixels with the same    intensity level are stacked in bars along the vertical axis. The    higher the bar the greater number of pixels at that intensity level.    The vertical bars toward the right side of the histogram indicate    pixels with higher intensities, while bars toward the left side of    the histogram indicate pixels with lower intensities.-   3. The mean and standard deviation of the Red intensities of the    Munsell N8 Matte Color sheet is measured as follows: Open a captured    image of the Munsell N8 Matte Color sheet using Adobe CS4. On the    left edge of the screen, select the “Rectangular Marquee Tool”. On    the top edge of the screen, set “Feather” to 0 px, “Style” to Fixed    size, “Width” to 5000 px, and “Height” to 3300 px. This defines a    rectangle containing 16500000 pixels whose size & shape matches the    size & shape of images of the Munsell N8 Matte Color sheet. Select    the image of the Munsell N8 Matte Color sheet using the “Rectangular    Marquee Tool”. Make sure the edges of the rectangle are within the    edges of the image of the Munsell N8 Matte Color sheet. Click the    circular symbol on the Histogram panel and make sure “Cache Level”    reads 1 in the Histogram panel. This measures and displays the mean    and standard deviation of the Red intensities the Munsell N8 Matte    Color sheet. Record these values.-   4. The mean and standard deviation of the Red intensities of the    built-in Munsell N8 reference within each image is measured as    follows: Open a captured image of the built-in Munsell N8 reference    within each image using Adobe CS4. On the left edge of the screen,    select the “Rectangular Marquee Tool”. On the top edge of the    screen, set “Feather” to 0 px, “Style” to Fixed size, “Width” to    5000 px, and “Height” to 800 px. This defines a rectangle containing    4000000 pixels whose size & shape matches the size & shape of the    built-in Munsell N8 reference within each image. Select the built-in    Munsell N8 reference within each image using the “Rectangular    Marquee Tool”. Make sure the edges of the rectangle are within the    edges of the built-in Munsell N8 reference within each image. Click    the circular symbol on the Histogram panel and make sure “Cache    Level” reads 1 in the Histogram panel. This measures and displays    the mean and standard deviation of the Red intensities of the    built-in Munsell N8 reference within each image. Record these    values.-   5. The mean and standard deviation of the Red intensities of each    reaction-zone on the peroxide test strip is measured as follows:    Open a captured image of the peroxide test strip using Adobe CS4. On    the left edge of the screen, select the “Rectangular Marquee Tool”.    On the top edge of the screen, set “Feather” to 0 px, “Style” to    Fixed size, “Width” to 1300 px, and “Height” to 1750 px. This    defines a rectangle containing 2275000 pixels whose size & shape    matches the size & shape of images of each reaction-zone on the    peroxide test strip. Select one of the two reaction-zones on the    peroxide test strip using the “Rectangular Marquee Tool”. Make sure    the edges of the rectangle are within the edges of the    reaction-zone. Click the circular symbol on the Histogram panel and    make sure “Cache Level” reads 1 in the Histogram panel. This    measures and displays the mean and standard deviation of the Red    intensities of one of the two reaction-zones on the peroxide test    strip. Record these values.    Method to Measure the Brookfield Viscosity of a Multi-Phase Oral    Care Composition or Hydrophobic Phase-   1. Transfer 40 to 50 ml of the multi-phase oral care composition or    hydrophobic phase into a 50 ml polypropylene conical tube (Falcon    brand catalog number REF 352098, Corning Science, Tamaulipas,    Mexico). If the multi-phase oral care composition or hydrophobic    phase exhibits macroscopic separation of one or more components    prior to transferring into the conical tube, mix the multi-phase    oral care composition or hydrophobic phase in a Speedmixer (for    example at 800 RPM for 2 minutes) and transfer into the conical tube    before it exhibits macroscopic separation of one or more components.    If the multi-phase oral care composition or hydrophobic phase has    macroscopic air-bubbles or voids: 1) Tap the conical tube on a hard    surface or mix the conical tube on a vortex mixer (for example    Vortex Genie 2 from Scientific Industries Inc. Bohemia, N.Y., or    Mini Vortexer from VWR Scientific Products) until it is    substantially free of macroscopic air-bubbles or voids or 2) Use a    different method to transfer the multi-phase oral care composition    into the conical tube such that it is substantially free of    macroscopic air-bubbles or voids.-   2. Allow the multi-phase oral care composition or hydrophobic phase    to equilibrate in the conical tube for at least 12 hours at the    desired temperature (for example −7° C., 4° C., 23° C., 25° C., 30°    C., 40° C., 50° C., or 60° C.).-   3. Confirm the viscometer (Brookfield 1/2RV DVII+Pro Viscometer) is    level, turn it on, and autozero it according to the instruction    manual.-   4. Attach the appropriate spindle (for example Spindle D, E, or F,    depending on the viscosity range of interest) and set the    appropriate speed (for example 0.5, 1.0, 2.0, 2.5, 4.0, 5.0, 10, 20,    50 and 100 RPM) for the Brookfield Viscosity anticipated to be    measured.-   5. Place the conical tube under the spindle, lower the spindle until    the t-bar is a few mm above the surface of the multi-phase oral care    composition, and center the conical tube under the spindle.-   6. Turn on the viscometer allow it to spin 3 to 5 rotations to    confirm the spindle spins freely without grazing the walls of the    conical tube. Turn on the helipath stand. When helipath lowers the    t-bar completely under the multi-phase oral care composition or    hydrophobic phase, turn on a timer set to 60 seconds. At 60 seconds    record the Brookfield Viscosity in cPs.-   7. Tap the conical tube on a hard surface or mix the conical tube on    a vortex mixer (for example Vortex Genie 2 from Scientific    Industries Inc. Bohemia, N.Y., or Mini Vortexer from VWR Scientific    Products) until it is substantially free of macroscopic air-bubbles    or voids, repeat steps-5-6 for a minimum of 3 measurements, with    about 10 minutes between measurements.-   8. Tap the conical tube on a hard surface or mix the conical tube on    a vortex mixer (for example Vortex Genie 2 from Scientific    Industries Inc. Bohemia, N.Y., or Mini Vortexer from VWR Scientific    Products) until it is substantially free of macroscopic air-bubbles    or voids, and repeat steps 2-7 for a second set od 3 measurements.    Calculate the average of all 6 measurements. This is the Brookfield    Viscosity of the multi-phase oral composition or hydrophobic phase.    To validate the above method, the Brookfield Viscosity of Example    I-B made according to the procedure specified herein must be    measured at 2.5 RPM with Spindle D at 23° C. and demonstrated to be    from 15,000 to 45,000 cPs.    Method to Measure the Yield Stress of a Multi-Phase Oral Care    Composition or Hydrophobic Phase    -   1. Transfer 40 to 50 ml of the multi-phase oral care composition        or hydrophobic phase into a 50 ml polypropylene conical tube        (Falcon brand catalog number REF 352098, Corning Science,        Tamaulipas, Mexico). If the multi-phase oral care composition or        hydrophobic phase exhibits macroscopic separation of one or more        components prior to transferring into the conical tube, mix the        multi-phase oral care composition or hydrophobic phase in a        Speedmixer (for example at 800 RPM for 2 minutes) and transfer        into the conical tube before it exhibits macroscopic separation        of one or more components. If the multi-phase oral care        composition or hydrophobic phase has macroscopic air-bubbles or        voids: 1) Tap the conical tube on a hard surface or mix the        conical tube on a vortex mixer (for example Vortex Genie 2 from        Scientific Industries Inc. Bohemia, N.Y., or Mini Vortexer from        VWR Scientific Products) until it is substantially free of        macroscopic air-bubbles or voids or 2) Use a different method to        transfer the multi-phase oral care composition into the conical        tube such that it is substantially free of macroscopic        air-bubbles or voids.    -   2. Allow the multi-phase oral care composition or hydrophobic        phase to equiliberate in the conical tube for at least 12 hours        at the desired temperature (for example −7° C., 4° C., 23° C.,        25° C., 30° C., 40° C., 50° C., or 60° C.).    -   3. Confirm the rheometer (Brookfield HAYR-1 Rheometer) is level,        turn it on, and autozero it according to the instruction manual.    -   4. Attach the appropriate spindle-vane (for example V72, V73, or        V75, depending on the viscosity range of interest) and set to        program for the specific spindle-vane being used. The program        parameters are specified below:

Spindle>> V-72 V-73 V-75 Yield Stress Range (Pa) 4-40 20-200 80-800Immersion Primary Primary Primary Pre-Sheer rpm 0 0 0 Pre-Sheer time 0 00 Zero Speed (rpm) 0.1 0.1 0.1 Wait Time (see) 30 30 30 Run Speed (rpm)0.1 0.1 0.3

-   -   5. Place the conical tube under the spindle-vane, and lower the        spindle-vane slowly into the sample, taking care to minimize any        disturbance to the sample this may cause. Continue lowering the        spindle-vane until the top surface of the sample is at the        primary immersion mark (bulge on the shaft) or secondary        immersion mark (notch on the spindle-vane). If the spindle-vane        is immersed to the secondary immersion mark, the value generated        by this method will need to be multiplied by two.    -   6. Run the program selected in step-4. Without removing the        spindle-vane run the program a total of 3 times. Record the 3        measurements. If the spindle-vane was immersed to the secondary        immersion mark, multiply each measurement by 2; and if the        spindle-vane was immersed to the primary immersion mark,        multiply each measurement by 1. Record the 3 calculated values.    -   7. Tap the conical tube on a hard surface or mix the conical        tube on a vortex mixer (for example Vortex Genie 2 from        Scientific Industries Inc. Bohemia, N.Y., or Mini Vortexer from        VWR Scientific Products) until it is substantially free of        macroscopic air-bubbles or voids, and repeat steps 2-6 for a        second set of 3 values. Calculate the average of all 6 values.        This is the Yield Stress of the multi-phase oral composition or        hydrophobic phase.

To validate the above method, the Yield Stress of Example I-B madeaccording to the procedure specified herein must be measured withspindle-vane V72 immersed to the secondary immersion mark at 23° C. anddemonstrated to be from 5 to 20 Pa.

Method to Measure the Slide Flow Distance of a Multi-Phase Oral CareComposition or Hydrophobic Phase

-   -   1. Prepare a piece of plexiglass to be 9″ long, 3″ wide, and ⅛″        thick. This is a holder for the microscope slides to be used in        following steps.    -   2. Place a microscope slide (VWR Micro Slides, Super Frost Plus,        25×75×1 mm, manufactured by VWR International, Radnor, Pa.;        purchased from VWR, Batavia, Ill., catalog number 48311-703)        with the frosted side facing down on the slide holder. Orient        the microscope slide such that the longest edge of the        microscope slide is parallel to the 3″ long edge of the holder        and square the microscope slide to the top 9″ long edge of the        holder. Repeat this for 3 microscope slides side-by-side on the        same holder. Note, the holder has room to hold up to 9        slides—making it possible to measure the slide flow distance of        up to 3 multi-phase compositions or hydrophobic phases at the        same time. Secure the top edge of the microscope slides to the        holder using 1″ wide tape (see FIG. 13).    -   3. While the slides and holder are horizontal, apply 0.10 to        0.12 gram of the multi-phase oral care composition or        hydrophobic phase to the clear section of each slide in a bead        about 20 to 25 mm long across the width of the slide within 5 mm        of the bottom edge of the frosted section of the slide (see        FIG. 13) using a syringe (3 ml BD Syringe with a Luer Lok tip,        REF 309657, purchased from VWR, Batavia, Ill.). Mark the initial        lowest point for each bead on the microscope slide.    -   4. Carefully tilt the holder (with the slides) such that the        slides are leaning at a 45 degree angle and hold it motionless        in this position for 60 seconds. This may done using a 45 degree        stand (see FIG. 14). At 60 seconds, carefully bring the holder        (with the slides) back to the horizontal position, and mark the        final lowest point for each bead on the microscope slide.    -   5. Measure the distance from the initial lowest point to the        final lowest point of the bead in mm. If the bead has flowed        down past the bottom edge of the slide, record the distance from        initial lowest point of the bead, and also note this as “greater        than” the distance from initial lowest point of the bead.    -   6. Repeat steps-2-5 for a minimum of 2 sets of 3 slides (minimum        total of 6 slides) per multi-phase oral care composition or        hydrophobic phase. Calculate the average distance measured on        all slides. This is the “slide flow distance” of the multi-phase        oral care composition or hydrophobic phase.

To validate the above method, the slide flow distance of 1) Example I-Bmade according to the procedure specified herein must be measured anddemonstrated to be from 0 mm to 15 mm, and, 2) the validationcomposition specified below made according to the procedure specifiedherein must be measured and demonstrated to be greater than 40 mm.

VALIDATION COMPOSITION FOR THE METHOD TO MEASURE THE SLIDE FLOW DISTANCE(Wt %) 35% aqueous solution H₂O₂ ¹ 1.43 Sterile Filtered Water² 4.24Aerosol OT³ 1.00 Mineral Oil⁴ 93.33 ¹ultra Cosmetic Grade from Solvay,Houston, Texas ²Calbiochem catalog number 4.86505.1000 from EMDMillipore Corporation, Billerica, Massachusetts ³Aerosol OT-100 fromCytec Industries, Princeton, NJ ⁴Kaydol grade from Sonneborn LLC,Petrolia, PennsylvaniaProcedure to Make the Validation Composition for the Method to Measurethe Slide Flow DistanceA 50-gram batch of the validation composition is made according to thefollowing procedure:

-   -   a) The Aerosol OT and mineral oil are weighed into a Speedmixer        container (“Max 40 Long Cup Translucent”, item number 501 223Lt        from Flacktek Inc., Landrum, S.C.). The mixture is heated in a        convection oven at 60 C and swirled to dissolve the Aerosol OT        in the mineral oil.    -   b) In a separate plastic container, 42.4 grams of sterile        filtered water and 14.3 grams of 35% aqueous solution of H₂O₂        are weighed and swirled to dissolve the H₂O₂ into the water.        This diluted solution of H₂O₂ is heated in a convection oven at        60 C for about 10 minutes. 2.84 grams of this diluted solution        of H₂O₂ in water is weighed into the Speedmixer container.    -   c) The contents of the Speedmixer container are mixed at 800 RPM        for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2        minutes. The walls of the container are then scraped down with a        rubber spatula, and the contents are mixed a second time at 800        RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2        minutes. The walls of the container are then scraped down with a        rubber spatula, and the contents are mixed a third time at 800        RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2        minutes.        Method to Measure the Percent Macroscopic Separation of One or        More Components of a Multi-Phase Oral Care Composition    -   1. Transfer 50 ml of the multi-phase oral composition into a 50        ml polypropylene conical tube (Falcon brand catalog number REF        352098, Corning Science, Tamaulipas, Mexico). If the multi-phase        oral composition exhibits macroscopic separation of one or more        components prior to transferring into the conical tube, mix the        multi-phase oral composition in a Speedmixer (in a “Max 300 Long        Cup Translucent”, item number 501 218t from Flacktek Inc.,        Landrum, S.C.) (for example at 800 RPM for 2 minutes) and        transfer into the conical tube before it exhibits macroscopic        separation of one or more components. If the multi-phase oral        composition has macroscopic air-bubbles or voids: 1) Tap the        conical tube on a hard surface until it is free of macroscopic        air-bubbles or voids, or 2) Use a different method to transfer        the multi-phase oral composition into the conical tube such that        it is substantially free of macroscopic air-bubbles or voids.        Screw the cap onto the conical tube. Repeat for a total of three        conical tubes.    -   2. Position all three conical tubes in a vertical orientation        (for example in a test tube rack) with the conical end on the        bottom and the cap on top.    -   3. Allow all three conical tubes to stay undisturbed in the        vertical position in a room or chamber in which the air is        maintained at the temperature (for example −7° C., 4° C., 23°        C., 25° C., 30° C., 40° C., 50° C., or 60° C.) for the period of        time after which the macroscopic separation is to be measured.    -   4. At the end of period of time after which the macroscopic        separation is to be measured (for example 1 day, 2 days, 1 week,        2 weeks, 1 month, 2 months, 3 months, 6 months, 12 months, 18        months, or 24 months) in the vertical position, measure the        volume of material that has macroscopically separated on the        bottom of the conical tube (aided by the graduations on the        conical tube). If the volume of material that has        macroscopically separated on the bottom of the conical tube is        greater than 25 ml, measure the volume of material that has        macroscopically separated to the top of the conical tube.        -   Calculate the average volume of material that has            macroscopically separated in all three tubes.        -   Assess the tube to tube variability of the volume of            material that has macroscopically separated as follows: The            volume of material that has separated in each and every tube            must be within the range of +/−2.5 ml of the average. If the            volume of material that has separated in any one or more of            the tubes is outside the range of +/−2.5 ml of the average:            This is an indication of sample to sample variability            potentially due to macroscopic separation of one or more            components prior to transferring into the conical tubes, and            the method needs to be repeated starting at step-1 to            minimize sample to sample variability.    -   5. Calculate the percent macroscopic separation as: 100×(average        volume of material that has macroscopically separated measured        and calculated in step-4 DIVIDED by 50 ml).

To validate the above method, the percent macroscopic separation of oneor more components of the validation composition specified below must bemeasured and demonstrated to be from 6% to 10%.

VALIDATION COMPOSITION FOR METHOD TO MEASURE PERCENT MACROSCOPICSEPARATION (Wt %) 35% aqueous solution H₂O₂ ¹ 1.43 Sterile FilteredWater² 4.24 Aerosol OT³ 1.00 Mineral Oil⁴ 93.33 ¹ultra Cosmetic Gradefrom Solvay, Houston, Texas ²Calbiochem catalog number 4.86505.1000 fromEMD Millipore Corporation, Billerica, Massachusetts ³Aerosol OT-100 fromCytec Industries, Princeton, NJ ⁴Kaydol grade from Sonneborn LLC,Petrolia, PennsylvaniaProcedure to Make the Validation Composition for Method to MeasurePercent Macroscopic SeparationThree 50-gram batches of the validation composition are made accordingto the following procedure:

-   -   d) The Aerosol OT and mineral oil are weighed into a Speedmixer        container (“Max 40 Long Cup Translucent”, item number 501 223Lt        from Flacktek Inc., Landrum, S.C.). The mixture is heated in a        convection oven at 60 C and swirled to dissolve the Aerosol OT        in the mineral oil.    -   e) In a separate plastic container, 42.4 grams of sterile        filtered water and 14.3 grams of 35% aqueous solution of H₂O₂        are weighed and swirled to dissolve the H₂O₂ into the water.        This diluted solution of H₂O₂ is heated in a convection oven at        60 C for about 10 minutes. 2.84 grams of this diluted solution        of H₂O₂ in water is weighed into the Speedmixer container.    -   f) The contents of the Speedmixer container are mixed at 800 RPM        for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2        minutes. The walls of the container are then scraped down with a        rubber spatula, and the contents are mixed a second time at 800        RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2        minutes. The walls of the container are then scraped down with a        rubber spatula, and the contents are mixed a third time at 800        RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2        minutes.        Method to Measure the Mean Residual Peroxide Concentration of a        Composition Smeared on Teeth

-   1. Cut a circular disc (7.5 to 7.8 mm diameter×1.2 to 1.3 mm    thickness) out of the front surface of a human incisor tooth. Leave    the front surface intact but flatten the back surface that has been    cut out of tooth using sandpaper. Soak the tooth-disc in 15 to 20 ml    of water that meets USP specification in a glass vial for at least    24 hours. Take the tooth-disc out of the water and place it on a    fresh paper towel with the front surface facing upward.

-   2. Weigh 290 to 310 grams of water that meets USP specifications    into a cylindrical plastic container with a screw-top lid 82 to 107    mm in diameter×106 to 108 mm height (“Max 200 Long Cup Translucent”,    item number 501 220t from Flacktek, Landrum, S.C.). Pre-heat the    water in the container with the lid screwed on tight in a convection    oven with air temperature at 33 C to 35 C for at least 12 hours.

-   3. Weigh 0.04 to 0.06 gram of the composition onto the tip of a    disposable lip gloss applicator (“Flocked Doe Foot Lip Gloss    Applicator” made of Nylon and Polystyrene, purchased from Qosmedix    Inc., Ronkonkoma, N.Y., catalog number 74111).

-   4. Smear the composition onto the front surface of the wet    tooth-disc by first rolling the tip of the lip gloss applicator    loaded with the composition on the front surface of the tooth-disc    to transfer the composition onto the tooth-disc and then fanning out    toward the circular edge.

-   5. Pick up the tooth-disc with a tweezer. Make sure the tweezer    touches only the circular edge of the tooth-disc and not the surface    of the tooth-disc smeared with the composition. Tilt the plastic    container and gently place the tooth-disc in the water on the    cylindrical wall of the container where the cylindrical wall and    flat bottom meet. Make sure the treated surface of the tooth-disc is    facing upward away from the cylindrical wall of the container.

-   6. Place the cylindrical container on a roller mixer (model number    TSRT9 by Techne purchased from VWR, Batavia, Ill., catalog number    89132-186; or item number 04750-30 from Cole-Parmer Inc., Vernon    Hills, Ill.). Turn on the roller mixer—this gently rotates the    container at 12 to 14 RPM. The tooth-disc should continue to remain    immersed in the water and the treated surface should continue to    face away from the rotating cylindrical wall. This rotating motion    causes the water to flow gently over the tooth-disc similar to the    gentle movement of saliva and other liquids over teeth in the mouth.

-   7. After 58 to 62 minutes shut off the roller mixer, take a fresh    peroxide test strip (supplied by EMD Millipore Corporation,    Billerica, Mass., supplier number 1.16974.0001; purchased from VWR,    Batavia, Ill., catalog number EM1.16974.0001) out of the container,    and start a timer.

-   8. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein.

-   9. Remove the tooth-disc from the water using a tweezer. As before,    make sure the tweezer touches only the circular edge of the    tooth-disc and not the surface of the tooth-disc smeared with the    composition. Place the tooth-disc on a gloved finger-tip. Make sure    the surface of the tooth-disc smeared with the composition is facing    upward away from the gloved finger-tip.

-   10. Place the peroxide test strip against the tooth-disc such that    one of the reaction-zones contacts the surface of the tooth-disc    with the residual composition. Pinch the peroxide test strip against    the tooth-disc between thumb and forefinger and apply firm finger    pressure between thumb and forefinger for 2 to 3 seconds.

-   11. Move the peroxide test strip to a clean area of a paper towel.    Place a filter paper (Whatman Grade 1 Qualitative Filter Paper    Standard Grade, circle, 90 mm, supplier number 1001-090; purchased    from VWR, Batavia, Ill., catalog number 28450-081) on top of the    test strip. Apply finger pressure on top of the filter paper. Pull    the peroxide test strip out from under the filter paper (while    maintaining finger pressure on the filter paper) in a single stroke    such that excess gel is wiped off onto the filter paper and paper    towel. Make sure the reaction-zones do not get dislodged from the    peroxide test strip.

-   12. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein.

-   13. Steps 7 to 12 must be completed within 3 minutes on the timer.

-   14. Repeat steps 1 to 13 for a minimum of twelve teeth.

-   15. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the Red intensities of    the strip of Munsell N8 Matte Color sheet attached to the holder    that serves as a built-in Munsell N8 reference within each image.    The mean R value intensity of the built-in Munsell N8 reference    within each image should be from 204 to 212 and the standard    deviation should be no more than 3.

-   16. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean of the Red intensities of the reaction-zone on all    peroxide test strips at BASELINE (before pressing against the    tooth-disc).

-   17. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean of the Red intensities of same the reaction-zone on    all peroxide test strips AFTER pressing against the tooth-disc.

-   18. The mean residual peroxide concentration of a composition    smeared on teeth is calculated as follows: First, calculate the mean    baseline R value intensity of each reaction-zone from step-16 MINUS    the mean R value intensity of the same reaction-zone after pressing    with the residual composition on the tooth-disc from step-17. Repeat    this calculation for all reaction-zones pressed against the    tooth-disc, and average the results. This is the mean residual    peroxide concentration of a composition smeared on teeth.    Method to Determine if a Composition is Easy to Manually Dispense    from a Tube    -   1. Select a foil laminate tube with the following dimensions:        -   a. Total length from tip of nozzle to bottom of barrel:            About 112 mm        -   b. Internal diameter of barrel: About 28 mm        -   c. Length of nozzle: About 21 mm        -   d. Internal diameter of nozzle: About 9.7 mm for half the            length of the nozzle attached to the barrel, and about 4.2            mm for the other half the of the nozzle leading to the exit            orifice of the nozzle.    -   2. Fill from about 35 to about 40 grams of the composition        through the bottom of the barrel into the tube from step-1. Seal        the bottom of the barrel using an ultrasonic sealer.    -   3. Allow the tube to stay undisturbed in a room or chamber in        which the air is maintained at the temperature (for example −7°        C., 4° C., 23° C., 25° C., 30° C., 40° C., 50° C., or 60° C.)        for the period of time after which the ease of dispensing is to        be measured.    -   4. Allow the tube to equilibrate at about 23° C. for at least a        day.    -   5. Pick up the tube between the thumb and fingers of one hand.        While holding the tube in the air, squeeze the tube firmly        between the thumb and fingers for about 10 seconds. Measure the        length of the bead of the composition dispensed out of the        nozzle of the tube.    -   6. The composition is considered easy to dispense manually from        a tube after the specified period of time at the specified        temperature if at least 1 inch of product is dispensed in        step-5.

Examples

The following non-limiting examples further describe preferredembodiments within the scope of the present invention. Many variationsof these examples are possible without departing from the scope of theinvention. All examples were performed at room temperature (RT) andatmospheric pressure unless stated otherwise.

TABLE 1 EXAMPLE I Weight %* A B C D E F 35% aqueous 15 8.5714 5 2.5 1.58.5714 solution of H₂O₂ ¹ PEG-20 1 1 1 1 1 3.43 Sorbitan monolaurate(Tween 20)² Mineral oil³ 84 90.4286 94 96.5 97.5 87.9986 % H₂O₂ 5.25 31.75 0.875 0.525 3 % Aqueous 16 9.5714 6 3.5 2.5 12.0014 phase %Hydrophobic 84 90.4286 94 96.5 97.5 87.9986 phase % Aqueous 12.83417.57190 4.7147 2.7433 1.9610 9.5893 phase by volume % Hydrophobic87.1659 92.4290 95.2853 97.2567 98.0390 90.4107 phase by volume ¹Ultracosmetic grade 35% from Solvay, Houston, TX ²Tween20-LQ-(AP) from CrodaInc. Edison, NJ ³Kaydol grade from Sonneborn LLC., Parsippany, NJ *% wtof total multi-phase composition unless otherwise indicated

TABLE 2 EXAMPLE II-V Example II Example III Example IV Example VComponent (wt %) (wt %) (wt %) (wt %) 35% aqueous  2.8571¹  8.5714² 8.5714²  8.5714² solution of H₂O₂ PEG-20 Sorbitan 1    1    1    1   monolaurate (Tween 20)³ Mineral oil  96.1429⁴   90.4286⁵  45.2143  —Petrolatum⁶ — — 45.2143  — Mineral Oil (and) — — — 90.4286 Ethylene/Propylene/ Styrene Copolymer (and) Butylene/ Ethylene/StyreneCopolymer⁷ % H₂O₂ 0.5   3    3    3    % Aqueous phase 3.8571 9.57149.5714 9.5714 % Hydrophobic 96.1429  90.4286  90.4286  90.4286  phase¹Ultra cosmetic grade 35% from Solvay, Houston, TX diluted with water(1:1 17.5% H₂O₂) ²Ultra cosmetic grade 35% from Solvay, Houston, TX³Tween20-LQ-(AP) from Croda Inc. Edison, NJ ⁴Kaydol grade from SonnebornLLC., Parsippany, NJ ⁵Hydrobrite HV grade from Sonneborn LLC.,Parsippany, NJ ⁶G-2218 Grade from Sonneborn, LLC., Parsippany, NJ⁷Versagel grade M 750 from Penreco Inc., Karns City, PABatches of Examples I, II, and III were made according to the followingprocedure:

-   -   1. The Tween 20 and aqueous solution of H₂O₂ were weighed into a        Speedmixer container (Max 300 Long Cup Translucent item number        501 218t or Max 300×Long Cup Translucent item number 501 217t,        for the 150-gram and 250-gram batches, and Max 200 Long Cup        Translucent item number 501 220t for the 50-gram batches, all        containers from Flacktek Inc., Landrum, S.C.) and mixed by        manually swirling the container until dissolved.    -   2. The mineral oil was added in portions (see table below,        generally starting with small portions and increasing to larger        portions) and mixed for about 1 to 2 minutes between portions        with a rubber spatula. An oil-in-water emulsion formed during        this step, and the composition developed a lotion-like semisolid        consistency.    -   3. Once all the mineral oil was added, the contents of the        Speedmixer container were mixed 3 times at 800 RPM for 2 minutes        each time in a Speedmixer.        A batch of Example IV was made according to the following        procedure:    -   1. The Tween 20 and aqueous solution of H₂O₂ were weighed into a        Speedmixer container (Max 300 Long Cup Translucent, item number        501 218t from Flacktek Inc., Landrum, S.C.) and mixed by        manually swirling the container until dissolved.    -   2. 30 grams of mineral oil was added in 2 portions of about 15        grams each and mixed for about 1 to 2 minutes between portions        with a rubber spatula. Separately, 44.61 grams of mineral oil        and 80 grams of petrolatum were blended together after heating        to about 80 C in a convection oven. 105.44 grams of this blend        was then added in a portions (increasing from about 13 grams to        about 33 grams per portion) and mixed for about 1 to 2 minutes        between portions with a rubber spatula. The speedmixer container        was immersed in water at 60 C during mixing, and the blend was        re-heated to 75 C to 80 C after the first two portions.    -   3. The contents of the Speedmixer container were mixed 2 times        at 800 RPM for 2 minutes each time in a Speedmixer.        A batch of Example V was made according to the following        procedure:    -   1. The Tween 20 and aqueous solution of H₂O₂ were weighed into a        Speedmixer container (Max 300 Long Cup Translucent, item number        501 218t from Flacktek Inc., Landrum, S.C.) and mixed by        manually swirling the container until dissolved.    -   2. The Versagel was added in a portions (see table below,        generally starting with small portions and increasing to larger        portions) and mixed for at least 2 minutes between portions with        a rubber spatula.        -   Once all the Versagel was added, the contents of the            Speedmixer container were mixed 3 times at 800 RPM for 2            minutes each time in a Speedmixer.

EXAMPLE Batch Approximate NUMBER size (g) portion size (g) I-A 150  10to 25  I-B Batch-1 150  25 Batch-2 150  15 to 25  Batch-3 250  23 to 51 Batch-4 150  20 to 25  Batch-5 150  20 to 25  Batch-6 150  20 to 25 Batch-7 250  5 to 20 Batch-8 250  5 to 20 I-C 150  5 to 10 I-D 150  2 to10 I-E 150  2 to 10 I-F 50 10 II 150  4 to 15 III 150  25 IV 150  12 to33  V 150  5 to 10

TABLE 3 COMPARATIVE EXAMPLES COMPARATIVE EXAMPLE I-IV I II III IV (wt %)(wt %) (wt %) (wt %) 35% aqueous solution of 25     8.5714  8.5714 8.5714 H₂O₂ ¹ PEG-20 Sorbitan  1    — —  3.43  monolaurate (Tween 20)²PEG-20 Sorbitan —  3.43  — — monostearate (Tween 60)³ PEG-20 Sorbitan ——  3.43  — monopalmitate (Tween 40)⁴ Mineral oil⁵ 74    87.9986 87.998687.9986 % H₂O₂  8.75   3     3     3    % Aqueous phase 26    12.001412.0014 12.0014 % Hydrophobic phase 74    91.3286 87.9986 87.9986 %Aqueous phase by 21.3475 — — — volume % Hydrophobic phase by 78.6525 — —— volume ¹35% Aqueous Solution Ultra cosmetic grade from Solvay,Houston, TX ²Tween20-LQ-(AP) from Croda Inc. Edison, NJ ³Tween60-LQ-(AP)from Croda Inc. Edison, NJ ⁴Tween40-LQ-(AP) from Croda Inc. Edison, NJ⁵Kaydol grade from Sonneborn LLC., Parsippany, NJ

TABLE 4 COMPARATIVE EXAMPLES V-VIII V VI VII VIII (wt %) (wt %) (wt %)(wt%) 35% aqueous solution of 8.5714 8.6055  8.571 8.5714 H₂O₂ ¹ PEG-20Sorbitan — — — 1    monolaurate (Tween 20)⁶ Sorbitan monolaurate 1    —— — (Span 20)² Sorbitan monopalmitate —  0.02876 — — (Span 40)³ Mineraloil⁴ 90.4286  — — 90.4286  Petrolatum⁵ — 91.3658  91.429 — % H₂O₂ 3   3.0119 3   3    % Aqueous phase 8.5714 8.6055  8.571 9.5714 %Hydrophobic phase 91.4286  91.3945  91.429 90.4286  ¹Ultra cosmeticgrade 35% from Solvay, Houston, TX ²Span20-LQ-(AP) from Croda Inc.Edison, NJ ³5pan 40 from Croda Inc., Edison, NJ, USA. ⁴Hydrobrite HVgrade from Sonneborn LLC., Parsippany, NJ ⁵G-2218 Grade from Sonneborn,LLC., Parsippany, NJ ⁶Tween20-LQ-(AP) from Croda Inc. Edison, NJBatches of Comparative Examples I, II, and III, were made according tothe following procedure:

-   -   1. The Tween 20, Tween 40, or Tween 60, was weighed into a        Speedmixer container (Max 300 Long Cup Translucent, item number        501 218t from Flacktek Inc., Landrum, S.C.) followed by the        aqueous solution of H₂O₂. The batch of Comparative Examples I        and II were mixed by manually swirling the container until        dissolved. The batch of Comparative Example III was vigorously        mixed with a rubber spatula until it was dissolved.    -   2. The mineral oil was added in portions (see table below) and        mixed for about 1 to 2 minutes between portions with a rubber        spatula.    -   3. Once all the mineral oil was added, the contents of the        Speedmixer container were mixed 3 times at 800 RPM for 2 minutes        each time in a Speedmixer.

COMPARATIVE Approximate EXAMPLE Batch size portion size NUMBER (g) (g) I150  10  II 150  25  III 150  25  IV 50 All mineral oil added in 1single portion V 150  n/a VI 250  n/a VII 250  n/a VIII 150  2A batch of Comparative Example IV was made according to the followingprocedure:

-   -   1. The Tween 20 was weighed into a Speedmixer container (Max 200        Long Cup Translucent item number 501 220t from Flacktek Inc.,        Landrum, S.C.) followed by the aqueous solution of H2O2, and        mixed by manually swirling the container until dissolved.    -   2. All the mineral oil was weighed into the Speedmixer container        in 1 single portion.    -   3. Once the mineral oil was added, the contents of the        Speedmixer container were mixed 1 time at 800 RPM for 2 minutes        followed by 1 time at 2600 RPM for 2 minutes in a Speedmixer.        A batch of Comparative Example V was made according to the        following procedure:    -   1. The Span 20 was weighed into a Speedmixer container (Max 300        Long Cup Translucent, item number 501 218t from Flacktek Inc.,        Landrum, S.C.) followed by the mineral oil, and mixed at 800 RPM        for two minutes in a Speedmixer until dissolved.    -   2. The aqueous solution of H₂O₂ was weighed into the Speedmixer        container.    -   3. The contents of the Speedmixer container were mixed 3 times        at 800 RPM for 2 minutes each time in a Speedmixer.        A batch of Comparative Example VI was made according to the        following procedure:    -   1. The Span 40 and petrolatum were weighed into a Speedmixer        container (Max 300 Long Cup Translucent, item number 501 218t        from Flacktek Inc., Landrum, S.C.). This container was then        placed in an convection oven set at 60 C until the temperature        of the contents was >58 C. The contents of the container were        then mixed at 2350 RPM for 30 seconds in a speedmixer to        dissolve the Span 40 into the petrolatum.    -   2. The container was then placed in an convection oven set at 34        C until the temperature of the contents was <38 C. The aqueous        solution of H2O2 was weighed into the Speedmixer container.    -   3. The contents of the Speedmixer container were mixed 3 times        at 800 RPM for 2 minutes each time in a Speedmixer.        A batch of Comparative Example VII was made as follows:    -   1. The petrolatum and 35% aqueous solution of H2O2 were added        into a Max 300 Long Speedmixer container (Flacktek Inc.,        Landrum, S.C.) and mixed in a SpeedMixer (Flacktek Inc.,        Landrum, S.C.) at 1600 RPM for 30 seconds.    -   2. The mixture was transferred to an empty 12.8 oz Caulk        Cartridge (McMaster Carr, Robbinsville, N.J.) and stored in a        refrigerator until the measured product temperature was 8° C.    -   3. The Caulk Cartridge was inserted into a Pneumatic Caulk Gun        (McMaster Can, Robbinsville, N.J.), and connected to the inlet        of a Microfluidizer model M-110Y (Microfluidics, Westwood, Mass.        02090). The outlet piping of the Microfluidizer was arranged        such that the product passed through only a F20Y Interaction        Chamber and several cm of piping before and after. The inlet        pressure to the Microfludizer was adjusted to 40 psig, and the        inlet pressure to the Caulk Cartridge was adjusted to 94 psig.        The final product was collected in a plastic container.        A batch of Comparative Example VIII was made according to the        following procedure:    -   1. The mineral oil was weighed into a Speedmixer container (Max        300 Long Cup Translucent, item number 501 218t from Flacktek        Inc., Landrum, S.C.).    -   2. The Tween 20 was weighed into a separate Speedmixer container        (“Max 40 Long Cup Translucent”, item number 501 223Lt from        Flacktek Inc., Landrum, S.C.) followed by the aqueous solution        of H2O2, and mixed by manually swirling the container until        dissolved. This mixture was then added in multiple portions (see        table above) to the mineral oil from step-1 and mixed for about        1 to 2 minutes between portions with a rubber spatula. The        composition remained liquid and did not develop a lotion-like        semisolid consistency during this step.    -   3. Once all the mixture of Tween 20 and aqueous solution of H₂O₂        was added, the contents of the Speedmixer container were mixed 3        times at 800 RPM for 2 minutes each time in a Speedmixer.

TABLE 5 Mean Peroxide Concentration Comparative Example VI Example I-B(Water-in-oil) (Jammed oil-in-water) (3% H2O2) (3% H2O2) Mean peroxide26.97 69.51 concentration smeared onto test strips

TABLE 6 Whitening Efficacy Comparative Example I-B Example VII (Jammedoil- (Water-in-oil) in-water) (90 minutes (60 minutes per treatment) pertreatment) Mean decrease in yellowness 2.185 2.908 (−Δb*) after 1treatment (measured the next day) Mean decrease in yellowness 3.3334.214 (−Δb*) after 2 treatments (measured the next day) Mean decrease inyellowness — 5.070 (−Δb*) after 3 treatments (measured the next day)

TABLE 7 Stability of Active Agents Example I-B Target for % H₂O₂remaining is 3% Oil-in-water emulsion Sample-1 Sample-2 Sample-3 % H₂O₂remaining in sample 2.926 2.938 2.915 after 90 days at 40° C.

TABLE 8 Slide Flow Distance Measured according to the methods Slide flowspecified herein distance (mm) Example I-B 5 mm Validation compositionfor the method to >45 mm    measure the slide flow distance specifiedherein

TABLE 9 Yield Stress Measured according to the method Yield Stress (Pa)specified herein Example I-B 12

TABLE 10 Water Dispersibility and Whitening Efficacy Comparative ExampleVII Example I-B (Water-in-oil) (Oil-in-water) (90 minutes (60 minutesper treatment) per treatment) Water-dispersibility (%) measured 2 70 according to the method specified herein at 23° C. Mean decrease inyellowness (−Δb*) after 1 treatment    2.185   2.908 (measured the nextday) Mean decrease in yellowness (−Δb*) after 2 treatments    3.333  4.214 (measured the next day) Mean decrease in yellowness (−Δb*) after3 treatments —   5.070 (measured the next day)

TABLE 11 Brookfield Viscosity of Example I-B Brookfield Viscosity (cPs)Example I-B 29,000¹    Hydrophobic Phase (Mineral Oil) 170²  AqueousPhase (Plus H₂O₂ and Tween 20) 22² ¹Using spindle D, 2.5 RPM ²Belowdetection limit for spindle D at 2.5 RPM, measured using spindle D at100 RPM

TABLE 12 Yield Stress of Example I-B Yield Stress (Pa) Example I-B 12Hydrophobic Phase (Mineral Oil) <Detection Limit of 4 Aqueous Phase(Plus H₂O₂ and Tween 20) <Detection Limit of 4

TABLE 13 D[4,3] equivalent-diameter of regions of hydrophobic phase ofExamples I-A, I-B, I-C, and I-D. I-A I-B I-C I-D D[4,3]equivalent-diameter of 50 23 12 4 regions of hydrophobic phase measuredaccording to the method specified herein at 23° C. (microns) % Aqueousphase 16 9.5714 6 3.5 % Hydrophobic phase 84 90.4286 94 96.5

TABLE 14 D[4,3] equivalent-diameter of regions of hydrophobic phase ofExamples I-B and I-F. I-B I-F D[4,3] equivalent-diameter of regions of23 9 hydrophobic phase measured according to the method specified hereinat 23° C. (microns) % Emulsifier 1 3.4

FIG. 1A-1E show the stable jammed oil-in-water emulsions of ExampleIA-IE. These compositions are shown in TABLE 1. In contrast, FIG. 2,shows a high internal phase oil-in-water emulsion that demonstratedmacroscopic separation. Importantly and unexpectedly, Examples 1A-1E(≥84% hydrophobic phase) all had a higher proportion of hydrophobicphase than Comparative Example I (74% hydrophobic phase).

FIG. 3A-3E are microscopic images of the stable jammed oil-in-wateremulsions. Examples IA-IE. In these images, the hydrophobic phaseappears as large regions with a thin region of continuous aqueous phasewith hydrogen peroxide. In certain embodiments, as the concentration ofthe hydrophobic phase passes the jamming concentration, the ability forhydrophobic regions to move becomes less as hydrophobic regionsinfluence the shape of adjacent or neighboring regions. This is seen inFIG. 3A-3E with the regions pressing against one another resulting inpolyhedral shapes instead of spherical droplets. As seen in the images,Example I-A had minimal macroscopic separation and Examples I-B to I-Ehad no macroscopic separation after 2 days at 60° C.

FIG. 4A (Comparative Example II) shows the macroscopic separation of ahigh internal phase oil-in-water emulsion when 3.43% of Tween 60 wasused as the emulsifier. FIG. 5 (Comparative Example III) shows themacroscopic separation of a high internal phase oil-in-water emulsionwhen Tween 40 was used as the emulsifier. In contrast, FIG. 4B (ExampleIF) shows a stable jammed oil-in-water emulsion when using Tween 20 asthe emulsifier.

FIG. 6A (Comparative Example IV) shows the macroscopic separation of ahigh internal phase oil-in-water emulsion while FIG. 6B (Example IF)shows a stable jammed oil-in-water emulsion. As shown in TABLE 1 andTABLE 3, Comparative Example IV and Example IF are identical except inthe method of making. In Comparative Example IV, the hydrophobic phasewas added in one single portion to the aqueous phase. In contrast,Example IF was made by adding the hydrophobic phase in multiple portionswith mixing in between added portions.

FIG. 7 shows that Example II is a stable jammed oil-in-water emulsionupon preparation. It appears as a cohesive semisolid bead when dispensedfrom a tube.

FIG. 8A shows the macroscopic separation of Comparative Example V whenSpan 20 was used as the emulsifier, while FIG. 8B shows a stable jammedoil-in-water emulsion of Example III when Tween 20 was used as anemulsifier. Example III showed no macroscopic separation after sevenmonths at 23° C.

FIG. 9A shows a microscopic image of Comparative Example VI, whichcomprises a water-in-oil emulsion. FIG. 9A shows discrete droplets ofaqueous phase dispersed in the hydrophobic phase. In contrast, FIG. 9Bshows the stable jammed oil-in-water emulsion of Example IB. FIG. 9Bshows discrete regions of hydrophobic phase with a thin continuousaqueous phase comprising the oral care active, which is hydrogenperoxide.

FIG. 10A shows a microscopic image of Comparative Example VII awater-in-oil emulsion with discrete droplets of aqueous phase dispersedin the hydrophobic phase. In contrast, FIG. 10B shows Example IB as ajammed oil-in-water emulsion with regions of oil dispersed in theaqueous phase. Example IB and Comparative Example VII only differ inthat Example IB comprises 1% of Tween 20 emulsifier while ComparativeExample VII has no emulsifier.

FIG. 11 shows Example IB as a stable jammed oil-in-water emulsion after90 days at 40° C. TABLE 7 shows that there is virtually no loss of H₂O₂over the 90 days at 40° C., which indicates that Example IB is verystable to reactivity and macroscopic separation.

FIGS. 12A and 12B show the surprisingly high decrease in yellownessafter 1 single treatment with Example I-B (delivered on a tray andcombined with electromagnetic radiation as specified herein).

FIG. 13 shows 1) a holder for the microscope slides, 2) 9 microscopeslides, 3) tape securing the slides to the holder, and 4) a samplesketch of a bead of a multi-phase oral care composition or hydrophobicphase applied to one of the slides.

FIG. 14 shows 3 beads for 2 batches of Example I-B, and 3 beads of thevalidation composition for the slide flow method specified herein afterit has been tilted at 45 degrees for 60 seconds. This image shows thatthe beads have barely flowed down the slides for Example IB, but flowedall the way to the bottom of the slide for the validation compositionfor the slide flow method specified herein. This indicates that thestable jammed oil-in-water emulsions will stay in place while in adelivery carrier.

FIG. 15 shows the template and a coverslip that can be used to load amulti-phase composition of the present invention for observation under amicroscope

FIG. 16 A shows Comparative Example VIII and FIG. 16B shows Example I-B.Importantly, as shown in TABLEs 1 and 4, are identical in compositionexcept for the method of making. In Comparative Example VIII, theaqueous phase was added to the hydrophobic phase, which led tomacroscopic separation less than one hour after addition. In contrast,in Example I-B, the hydrophobic phase was portion-wise added to theaqueous phase while mixing between each addition of a portion of thehydrophobic phase. Example I-B is shown in FIG. 16B as a jammedoil-in-water emulsion that has shown no macroscopic separation afterstorage at room temperature (˜23° C.) for seven months.

TABLES 1 and 2 show inventive examples, while TABLES 3 and 4 showcomparative examples, as described herein.

TABLE 5 shows the mean peroxide of two samples comprising hydrogenperoxide. Even though both compositions had the same level of H₂O₂,Example IB which was a stable jammed oil-in-water emulsion delivered ahigher mean peroxide concentration smeared onto test strips thanComparative Example VI which was a water-in-oil emulsion.

TABLE 6 shows the whitening efficacy of several composition.Specifically, this table shows that even though 1) both compositions hadthe same level of H₂O₂ (3%), and, 2) the treatment time for Example I-Bwas shorter (60 minutes Vs. 90 minutes), Example I-B, which comprises anoil-in-water emulsion, delivered a higher mean decrease in yellownessthan Comparative Example VII which comprises a water-in-oil emulsion

TABLE 8 shows that even though all the examples had the same level ofH2O2, Example I-B with the lowest Brookfield Viscosity delivered thehighest mean peroxide concentration smeared onto test strips. TABLE 9shows the yield stress for Example IB.

TABLE 10 shows that even though Example I-B, which comprises a stablejammed oil-in-water emulsion has a higher water-dispersibility, it alsodelivered a higher mean decrease in yellowness than Comparative ExampleVII which comprises a water-in-oil emulsion

TABLE 11 shows that Example I-B which comprises a stable jammedoil-in-water emulsion has a Brookfield Viscosity much higher than thehydrophobic phase and the aqueous phase from which it was made.

TABLE 12 shows that Example I-B which comprises a stable jammedoil-in-water emulsion has a Yield Stress higher than the hydrophobicphase and the aqueous phase from which it was made.

TABLE 13 shows that the D[4,3] equivalent-diameter of regions ofhydrophobic phase decreases as the percentage of hydrophobic phaseincreases and the percentage of aqueous phase of increases.

TABLE 14 shows that the D[4,3] equivalent-diameter of regions ofhydrophobic phase decreases as the percentage of emulsifier increases.

The microscope images, as described herein, were captured using thefollowing procedure to load the multi-phase oral care composition on themicroscope slide. In general, the sample was sandwiched between themicroscope slide and the coverslip, such that the sample was no morethan 100 microns thick. This was done by the following procedure:

-   -   1. Place a microscope slide (VWR Micro Slides, Super Frost Plus,        25×75×1 mm, manufactured by VWR International, Radnor, Pa.;        purchased from VWR, Batavia, Ill., catalog number 48311-703)        with the frosted side facing up on a clean working surface.    -   2. Carefully dab a disposable transfer pipet with a fine tip        (5.8 ml polyethylene, purchased from VWR, Batavia, Ill., catalog        number 414004-020) into the multi-phase oral care composition        taking care not to suction the composition into the pipet.    -   3. Transfer about 5 mg of the composition from the tip of the        transfer pipet to the surface of the microscope slide. This may        be done by gently tapping the tip of the transfer pipet on the        microscope slide.    -   4. Hold a microscope coverslip (VWR Micro Cover Glass, 22 mm×22        mm×generally about 130 microns thick, purchased from VWR,        Batavia, Ill., catalog number 48366 067) over the sample and        center it. Gently drop the coverslip onto the sample.    -   5. Place a template (about 230 microns thick, FIG. 15) with a        square hole cut in the middle around the coverslip, taking care        not to touch the coverslip. Place a second microscope slide on        top of the coverslip and press down against the template. This        will ensure that the sample is no more than 100 microns thick.        Note, the thickness of the sample may be less than 100 microns        in certain cases, depending on the viscosity and surface tension        of the sample.    -   6. The sample is now ready to be viewed under a microscope        within about 10 minutes.

The bleaching efficacy of Example I-B was measured per the clinicalprotocol disclosed herein. Specifically, the bleaching efficacy ofExample-I-B was measured in a single-center, single-treatment clinicalstudy with 10 adults who had never had a professional, over-the-counteror investigational tooth bleaching treatment. All participants were atleast 18 years old, had all four measurable maxillary incisors, and hadno self-reported tooth sensitivity. Participants were assigned to thefollowing treatment group:

-   -   Example I-B (10 participants, mean L* of 73.848 and mean b* of        15.172)        The participants were treated once daily for 3 days, as        described herein.

The participants demonstrated a statistically significant (p<0.0001)reduction in yellowness (−Δb*) at all tested time-points relative toBaseline.

The bleaching efficacy of Comparative Example VII was measured in acontrolled, single-center, clinical study with 11 adults who had neverhad a professional, over-the-counter or investigational tooth bleachingtreatment. All participants were at least 18 years old, had all fourmeasurable maxillary incisors, and had no self-reported toothsensitivity. Participants were assigned to the following treatmentgroup:

-   -   Comparative Example VII (11 participants, mean L* of 73.667 and        mean b* of 15.138)        The bleaching efficacy of Comparative Example VII was measured        per the clinical protocol disclosed herein with the following        modifications:    -   The maxillary anterior teeth of the participants were treated        with the multi-phase oral care composition for 90 minutes        (instead of 60 minutes) once daily using a disposable        polyethylene strip as the delivery carrier. A disposable strip        was used instead of a tray because Comparative Example VII is        not as easy to rinse from a tray as Example I-B. The        polyethylene strips were 66 mm×15 mm in size and 0.0178 mm        thick. From 0.6 g to 0.8 g of the multi-phase oral care        composition was applied across each strip of polyethylene prior        to applying to the maxillary anterior teeth. Within these 90        minutes, the composition was re-applied to the teeth using a new        strip every 30 minutes for a total of 3×30-minute applications.    -   Within each 30-minute application, a trained hygienist applied        electromagnetic radiation toward the facial surfaces of the        maxillary anterior teeth during the last 10 minutes. The three        30-minute applications were applied back-to-back for a total of        90 minutes per treatment, once daily. The electromagnetic        radiation was directed toward the teeth through the strip and        through the oral composition.    -   Digital images were collected according to the clinical protocol        at baseline and the day after 1 and 2 treatments.

The electromagnetic radiation was delivered using the source ofelectromagnetic radiation described herein in the section titled“Clinical protocol”. The intensity of the electromagnetic radiation from400 nm to 500 nm measured at the central axis of each cone ofelectromagnetic radiation exiting at the exit surface of the transparentwindow through which the electromagnetic radiation passes toward themaxillary anterior teeth was measured to be from about 175 mW/cm² toabout 225 mW/cm², as measured by the method disclosed herein. Once 90minutes of treatment was completed the strip was removed. Theparticipants were treated once daily for 3 days.

The participants demonstrated a statistically significant (p<0.0001)reduction in yellowness (−Δb*) at all tested time-points relative toBaseline. TABLE 6 shows the results.

The results in TABLE 6 show that, 1) even though both compositions hadthe same level of H₂O₂, and 2) the treatment time for the Exampleoil-in-water emulsion was shorter (60 minutes Vs. 90 minutes), itdelivered a higher mean decrease in yellowness than the ComparativeExample water-in-oil emulsion. Specifically, 1) after 1×60-minutetreatment, Comparative Example VII delivered a mean decrease inyellowness of 2.185 while Example I-B (oil-in-water emulsion) delivereda mean decrease in yellowness of 2.908—this is about 33% more efficacyin 33% less time, and 2) after 2×60-minute treatments, ComparativeExample VII delivered a mean decrease in yellowness of 3.333 whileExample I-B (oil-in-water emulsion) delivered a mean decrease inyellowness of 4.214—this is about 26% more efficacy in 33% less time.These results are surprising because, 1) both compositions had the samelevel of H₂O₂ (3%), 2) the teeth were treated with 3×10 minuteselectromagnetic radiation with both compositions, and 3) the treatmenttime for the Example oil-in-water emulsion was 33% shorter (60 minutesVs. 90 minutes) than the Comparative Example water-in-oil emulsion.

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application and any patent application or patent to which thisapplication claims priority or benefit thereof, is hereby incorporatedherein by reference in its entirety unless expressly excluded orotherwise limited. The citation of any document is not an admission thatit is prior art with respect to any invention disclosed or claimedherein or that it alone, or in any combination with any other referenceor references, teaches, suggests or discloses any such invention.Further, to the extent that any meaning or definition of a term in thisdocument conflicts with any meaning or definition of the same term in adocument incorporated by reference, the meaning or definition assignedto that term in this document shall govern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. An oral care composition comprising jammedoil-in-water emulsion, the jammed oil-in-water emulsion comprising: (a)at least partially continuous aqueous phase; (b) discontinuoushydrophobic phase; (c) oral care active agent; and (d) emulsifier with ahydrophilic-lipophilic balance of from about 11 to about
 60. 2. The oralcare composition of claim 1, wherein the oral care composition comprisesfrom about 80% to about 99%, by weight of the composition, of thehydrophobic phase.
 3. The oral care composition of claim 1, wherein theoral care composition comprises from about 1% to about 20%, by weight ofthe aqueous phase, of the aqueous phase.
 4. The oral care composition ofclaim 1, wherein the oral care composition comprises from about 5% toabout 15%, by weight of the aqueous phase, of the aqueous phase.
 5. Theoral care composition of claim 1, wherein the aqueous phase comprisesthe oral care active agent.
 6. The oral care composition of claim 1,wherein the hydrophobic phase comprises the oral care active agent. 7.The oral care composition of claim 5, wherein the oral care active agentcomprises bleaching agent, anti-caries agent, anti-tartar agent,remineralization agent, wound healing agent, anti-inflammatory agent,antibacterial agent, metal ion source, anti-glycolytic agent, aminoacid, probiotic, prebiotic, postbiotic, polyphosphate, buffer,anti-sensitivity agent, or combinations thereof.
 8. The oral carecomposition of claim 7, wherein the oral care active agent compriseshydrogen peroxide.
 9. The oral care composition of claim 8, wherein theaqueous phase comprises from about 5% to about 67%, by weight of thecomposition, of the oral care active agent.
 10. The oral carecomposition of claim 1, wherein the oral care composition comprises fromabout 0.01% to about 10%, by weight of the composition, of theemulsifier.
 11. The oral care composition of claim 1, wherein theemulsifier comprises a polysorbate, an alkyl sulfate, or combinationsthereof.
 12. The oral care composition of claim 1, wherein theemulsifier comprises polysorbate 20, polysorbate 40, sodium laurylsulfate, or combinations thereof.
 13. The oral care composition of claim1, wherein the emulsifier comprises one or more hydrophobic tails, theone or more hydrophobic tails having from about 6 to about 20 carbonatoms.
 14. The oral care composition of claim 13, wherein the one ormore hydrophobic tails has up to 4 branches.
 15. The oral carecomposition of claim 1, wherein the emulsifier comprises a blend ofmultiple emulsifiers.
 16. The oral care composition of claim 1, whereinthe emulsifier is hydrophilic, miscible with water, immiscible withmineral oil, or combinations thereof.
 17. A method of applying the oralcare composition of claim 1 to at least one tooth of a consumer.
 18. Amethod of applying the oral care composition of claim 1 to at least onetooth of a consumer in a delivery carrier.
 19. The method of claim 18,wherein the delivery carrier is a tray or strip.
 20. A jammedoil-in-water emulsion composition comprising a discontinuous hydrophobicphase prepared by a process comprising the steps of: (a) combining aportion of hydrophobic composition with aqueous composition, the aqueousphase comprising oral care active agent and emulsifier with ahydrophilic-lipophilic balance of from about 11 to about 60; (b) mixingthe portion of hydrophobic composition and aqueous composition; and (c)repeating steps (a) and (b) until the entire hydrophobic composition hasbeen combined with the aqueous composition.
 21. The composition of claim20, wherein the oral care active agent comprises hydrogen peroxide. 22.The composition of claim 20, wherein the hydrophobic composition iscombined with the aqueous composition by portion-wise addition, gradualaddition, or combinations thereof.
 23. The composition of claim 20,wherein the oral care active agent comprises bleaching agent,anti-caries agent, anti-tartar agent, remineralization agent, woundhealing agent, anti-inflammatory agent, antibacterial agent, metal ionsource, anti-glycolytic agent, amino acid, probiotic, prebiotic,postbiotic, polyphosphate, buffer, anti-sensitivity agent, orcombinations thereof.
 24. The composition of claim 20, wherein thecomposition comprises from about 0.01% to about 10%, by weight of thecomposition, of the emulsifier.
 25. The composition of claim 20, whereinthe emulsifier comprises a polysorbate, an alkyl sulfate, orcombinations thereof.
 26. The composition of claim 20, wherein theemulsifier comprises polysorbate 20, polysorbate 40, sodium laurylsulfate, or combinations thereof.
 27. The composition of claim 20,wherein the emulsifier comprises one or more hydrophobic tails, the oneor more hydrophobic tails having from about 6 to about 20 carbon atoms.28. The composition of claim 27, wherein the one or more hydrophobictails has up to 4 branches.
 29. A jammed oil-in-water emulsioncomposition comprising a discontinuous hydrophobic phase prepared by aprocess comprising the steps of combining hydrophobic composition withaqueous composition in a continuous or pulsed fashion while continuouslystirring the hydrophobic composition and the aqueous composition untilall of the hydrophobic composition has been combined with the aqueouscomposition, wherein the aqueous phase comprises oral care active agentand emulsifier with a hydrophilic-lipophilic balance of from about 11 toabout
 60. 30. The composition of claim 29, wherein the oral care activeagent comprises bleaching agent, anti-caries agent, anti-tartar agent,remineralization agent, wound healing agent, anti-inflammatory agent,antibacterial agent, metal ion source, anti-glycolytic agent, aminoacid, probiotic, prebiotic, postbiotic, polyphosphate, buffer,anti-sensitivity agent, or combinations thereof.
 31. The composition ofclaim 29, wherein the composition comprises from about 0.01% to about10%, by weight of the composition, of the emulsifier.
 32. Thecomposition of claim 29, wherein the emulsifier comprises a polysorbate,an alkyl sulfate, or combinations thereof.
 33. The composition of claim29, wherein the emulsifier comprises polysorbate 20, polysorbate 40,sodium lauryl sulfate, or combinations thereof.
 34. The composition ofclaim 29, wherein the emulsifier comprises one or more hydrophobictails, the one or more hydrophobic tails having from about 6 to about 20carbon atoms.
 35. The composition of claim 34, wherein the one or morehydrophobic tails has up to 4 branches.